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Drug Discovery and Evaluation: Pharmacological Assays pp 1553–1592Cite as

Animal Models of Neurological Disorders

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Abstract

Huntington’s disease is a neurological disorder characterized by loss of striatal neurons and the motor signs of dyskinesia, dystonia, and chorea, as well as complex neuropsychiatric changes (Hayden 1981). Brouillet et al. (1999) reviewed the different aspects of the replicating Huntington’s disease phenotype in experimental animals. There is at present no effective therapy against this disorder. The gene responsible for the disease has been cloned and the molecular defect identified as an expanded polyglutamine tract in the N-terminal region of a protein, named huntingtin (Landles and Bates 2004; Li and Li 2004). Huntingtin interacts with a number of proteins and it has been suggested that alterations in glycolysis, vesicle trafficking, or apoptosis play a role in the pathophysiology of Huntington’s disease.

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References and Further Reading

Huntington’s Disease

  • Brouillet E, Condé F, Beal MF, Hantraye P (1999) Replicating Huntington’s disease phenotype in experimental animals. Prog Neurobiol 59:427–468

    CAS  PubMed  Google Scholar 

  • Hayden MR (1981) Huntington’s chorea. Springer, Berlin/Heidelberg/New York

    Google Scholar 

  • Landles C, Bates GP (2004) Huntingtin and the molecular pathogenesis of Huntington’s disease. EMBO Rep 5:958–963

    PubMed Central  CAS  PubMed  Google Scholar 

  • Li SH, Li XJ (2004) Huntingtin and its role in neuronal degeneration. Neuroscientist 10:467–475

    CAS  PubMed  Google Scholar 

Nitropropionic Acid Animal Model of Huntington’s Disease

  • Beal MF, Brouillet E, Jenkins BG, Ferrante RJ, Kowall NW, Miller JM, Storey E, Srivastava R, Rosen BR, Hyman BT (1993) Neurochemical and histologic characterization of striatal excitotoxic lesions produced by the mitochondrial toxin 3-nitropropionic acid. J Neurosci 13:4181–4192

    CAS  PubMed  Google Scholar 

  • Borlongan CV, Koutouzis TK, Randall TS, Freeman TB, Cahill DW, Sanberg PR (1995) Systemic 3-nitropropionic acid: behavioral deficits and striatal damage in adult rats. Brain Res Bull 36:549–556

    CAS  PubMed  Google Scholar 

  • Borlongan CV, Koutouzis TK, Sanberg PR (1997a) 3-Nitropropionic acid animal model and Huntington’s disease. Neurosci Biobehav Rev 21:289–293

    CAS  PubMed  Google Scholar 

  • Borlongan CV, Koutouzis TK, Freeman TB, Hauser RA, Cahill DW, Sanberg PR (1997b) Hyperactivity and hypoactivity in a rat model of Huntington’s disease: the systemic 3-nitropropionic acid model. Brain Res Brain Res Protoc 1:253–257

    CAS  PubMed  Google Scholar 

  • Brouillet E, Jenkins BG, Hyman BT, Ferrante RJ, Kowall MW, Srivastava R, Roy DS, Rosen BR, Beal MF (1993) Agedependent vulnerability of the striatum to the mitochondrial toxin 3-nitropropionoic acid. J Neurochem 60:356–359

    CAS  PubMed  Google Scholar 

  • Guyot MC, Hantraye P, Dolan R, Palfi S, Maziére M, Brouillet E (1997) Quantificable bradykinesia gait abnormalities and Huntington’s disease-like striatal lesionsa in rats chronically treated with 3-nitropropionic acid. Neuroscience 79:45–56

    CAS  PubMed  Google Scholar 

  • Hantraye P, Riche D, Maziere M, Isacson O (1992) Intrastriatal transplantation of cross-species fetal striatal cells reduces abnormal movements in a primate model of Huntington’s disease. Proc Natl Acad Sci U S A 89:4187–4191

    PubMed Central  CAS  PubMed  Google Scholar 

  • Lastres-Becker I, de Miguel R, de Petrocellis L, Makriyannis A, di Marzo V, Fernandez-Ruiz J (2003) Compounds acting on the endocannabinoid and/or endovanilloid systems reduce hyperkinesia in a rat model of Huntington’s disease. J Neurochem 84:1097–1109

    CAS  PubMed  Google Scholar 

  • Lee WT, Chang C (2004) Magnetic resonance imaging and spectroscopy in assessing 3-nitrpropionic acid-induced brain lesions. an animal model of Huntington’s disease. Prog Neurobiol 72:87–110

    CAS  PubMed  Google Scholar 

  • Lee WT, Shen YZ, Chang C (2000) Neuroprotective effect of lamotrigine and MK-801 on rat brain lesions induced by 3-nitropropionic acid: evaluation by magnetic resonance imaging and in vivo proton magnetic resonance spectroscopy. Neuroscience 95:89–95

    CAS  PubMed  Google Scholar 

  • Matthews RT, Yang L, Jenkins BC, Ferrante RJ, Rosen BR, Kaddurah-Daouk R, Beal MF (1998) Neuroprotective effects of creatine and cyclocreatine in animal models of Huntington’s disease. J Neurosci 1(8):156–163

    Google Scholar 

  • Mittoux V, Joseph JM, Conde F, Palfi S, Dautry C, Poyot T, Bloch J, Deglon N, Ouary S, Nimchinsky EA, Brouillet E, Hof PR, Peschanski M, Aebischer P, Hantraye P (2000) Restoration of cognitive and motor function by ciliary neurotrophic factor in a primate model of Huntington’s disease. Hum Gene Ther 11:1177–1187

    CAS  PubMed  Google Scholar 

  • Palfi S, Ferrante RJ, Brouillet E, Beal MF, Dolan R, Guyot MC, Peschanski M, Hantraye P (1996) Chronic 3-nitropropionic acid treatment in baboons replicates the cognitive and motor deficits in Huntington’s disease. J Neurosci 16:3019–3025

    CAS  PubMed  Google Scholar 

  • Pubill D, Verdaguer E, Canudas AM, Sureda FX, Escubedo E, Camrasa J, Pallas M, Camis A (2001) Orphenadrine prevents 3-nitropropionic acid-induced neurotoxicity in vitro and in vivo. Br J Pharmacol 132:693–702

    PubMed Central  CAS  PubMed  Google Scholar 

  • Quary S, Bizat N, Altairac S, Ménétrat N, Mittoux V, Condé F, Hantraye P, Brouillet E (2000) Major strain differences in response to chronic systemic administration of the mitochondrial toxin 3-nitropropionic acid in rats: implications for neuroprotection studies. Neuroscience 97:521–530

    Google Scholar 

  • Tunez I, Montilla P, del Carmen-Munoz M, Feijoo M, Salcedo M (2004) Protective effect of melatonin on 3-nitropropionic acid-induced oxidative stress in synaptosomes in an animal model of Huntington’s disease. J Pineal Res 37:252–256

    CAS  PubMed  Google Scholar 

Quinolinic Acid Rat Model of Huntington’s Disease

  • Anderson KD, Panayotatos N, Corcoran TL, Lindsay RM, Wiegand SJ (1996) Ciliary neurotrophic factor protects striatal output neurons in an animal model of Huntington’s disease. Proc Natl Acad Sci U S A 93:7346–7351

    PubMed Central  CAS  PubMed  Google Scholar 

  • Araujo DM, Hilt DC (1997) Glial cell line-derived neurotrophic factor attenuates the excitotoxin-induced behavioral and neurochemical deficits in a rodent model of Huntington’s disease. Neuroscience 81:1099–1110

    CAS  PubMed  Google Scholar 

  • Beal MF, Kowall NW, Ellison DW, Mazurek MF, Swarz KJ, Martin JB (1986) Replication of the neurochemical characteristics of Huntington’s disease by quinolinic acid. Nature 321:168–171

    CAS  PubMed  Google Scholar 

  • Beal MF, Kowall NW, Swartz KJ, Ferrante RJ, Martin JB (1988) Systemic approaches to modifying quinolinic acid striatal lesions in rats. J Neurosci 8:3901–3906

    CAS  PubMed  Google Scholar 

  • Beal MF, Ferrante RJ, Swartz KJ, Kowall NW (1991) Chronic quinolinic acid lesions in rats closely resemble Huntington’s disease. J Neurosci 11:1649–1659

    CAS  PubMed  Google Scholar 

  • Bensadoun JC, de Almeida LP, Dreano M, Aebischer P, Deglon N (2001) Neuroprotective effect of interleukin-6 and IL6/IL6R chimera in the quinolinic acid rat model of Huntington’s disease. Eur J Neurosci 14:1753–1761

    CAS  PubMed  Google Scholar 

  • Burns LH, Pakzaban P, Deacon TW, Brownell AW, Tatter SB, Jenkins GB, Isacson O (1995) Selective putaminal excitotoxic lesions in non-human primates model the movement disorders of Huntington’s disease. Neuroscience 64:1007–1017

    CAS  PubMed  Google Scholar 

  • DiFiglia M (1990) Excitotoxic injury of the neostriatum: a model for Huntington’s disease. Trends Neurosci 13:286–289

    CAS  PubMed  Google Scholar 

  • Gianfriddo M, Corsi C, Melani A, Pèzzola A, Reggio R, Popoli P, Pedata F (2003) Adenosine A2A antagonism increases striatal glutamate outflow in the quinolinic acid rat model of Huntington’s disease. Brain Res 979:225–229

    CAS  PubMed  Google Scholar 

  • Hughes PE, Alexi T, Williams CE, Clark RG, Gluckman PD (1999) Administration of recombinant human activin-A has powerful neurotrophic effects on selected striatal phenotypes in the quinolinic acid lesion model of Huntington’s disease. Neuroscience 92:197–209

    CAS  PubMed  Google Scholar 

  • Lapchak PA, Jiao SJ, Collins F, Miller PJ (1997) Glial cell linederived neurotrophic factor: distribution and pharmacology in the rat following a bolus intraventricular injection. Brain Res 747:92–102

    CAS  PubMed  Google Scholar 

  • Lin LF, Doherty DH, Lile JD, Bektesch S, Collins P (1993) GDNF: a glial cell line-derived neurotrophic factor for midbrain dopaminergic neurons. Science 260:1130–1132

    CAS  PubMed  Google Scholar 

  • Nakao N, Grasbon-Frodl EM, Widner H, Brundin P (1996) DARPP-32-rich zones in grafts of lateral ganglionic eminence govern the extent of functional recovery in skilled paw reaching in an animal model of Huntington’ disease. Neuroscience 74:959–970

    CAS  PubMed  Google Scholar 

  • Nakao N, Ogura M, Nakai K, Itakura T (1999) Embryonic striatal grafts restore neuronal activity of the globus pallidus in a rodent model of Huntington’s disease. Neuroscience 88:469–477

    CAS  PubMed  Google Scholar 

  • Pérez-Navarro E, Arenas E, Marco S, Alberch J (1999) Intrastriatal grafting of GDNΒ-producing cell line protects striatonigral neurons from quinolinic acid excitotoxicity in vivo. Eur J Neurosci 11:241–249

    PubMed  Google Scholar 

  • Pérez-Navarro E, Canudas AM, Akerud P, Alberch J, Arenas E (2000a) Brain-derived neurotrophic factor, neurotrophin-3 and neurotrophin 4/5 prevent the death of striatal projection neurons in a rodent model of Huntington’s disease. J Neurochem 75:2190–2199

    PubMed  Google Scholar 

  • Pérez-Navarro E, Ãkerud P, Marco S, Canals JM, Tolosa E, Arenas E, Alberch J (2000b) Neurturin protects striatal neurons but not interneurons in a rat model of Huntington’s disease. Neuroscience 98:89–96

    PubMed  Google Scholar 

  • Reggio R, Pèzzzola A, Popoli P (1999) The intrastriatal injection of an adenosine Α2 receptor antagonist prevents frontal cortex EEG abnormalities in a rat model of Huntington’s disease. Brain Res 831:315–318

    CAS  PubMed  Google Scholar 

  • Ryu JK, Kim SU, McLarnon JG (2003) Neuroprotective effects of pyruvate in the quinolinic acid rat model of Huntington’s disease. Exp Neurol 183:700–704

    CAS  PubMed  Google Scholar 

  • Scattoni ML, Valanzano A, Popoli P, Pezzola A, Reggio R, Calamandrei G (2004) Progressive behavioral changes in the spatial open-field in the quinolinic acid rat model of Huntington’s disease. Behav Brain Res 152:375–383

    PubMed  Google Scholar 

  • Shear DA, Dong J, Gundy CD, Haik-Creguer KL, Dunbar GL (1998) Comparison of intrastriatal injections of quinolinic acid and 3-nitropropionic acid for use in animal models of Huntington’s disease. Prog Neuropsychopharmacol Biol Psychiatry 22:1217–1240

    CAS  PubMed  Google Scholar 

Transgenic Animal Models of Huntington’s Disease

  • Agrawal N, Pallos J, Slöepko N, Apostol BL, Bodai L, Chang LW, Chiang AS, Thompson LM, Marsh JL (2005) Identification of combinatorial drug regimens for treatment of Huntington’s disease using Drosophila. Proc Natl Acad Sci U S A 102:3777–3781

    PubMed Central  CAS  PubMed  Google Scholar 

  • Ainscough JF, John RM, Barton SC (2001) Production of YAC transgenic mice by pronuclear injection. Methods Mol Biol 181:55–65

    CAS  PubMed  Google Scholar 

  • Al Mahdawi S, Pinto RM, Ruddle P, Carroll C, Webster Z, Pook M (2004) GAA repeat instability in Friedreich ataxia YAC transgenic mice. Genomics 84:301–310

    CAS  PubMed  Google Scholar 

  • Ariano MA, Cepeda C, Calvert CE, Flores-Hernández J, Hernández-Echeagaray E, Klapstein GJ, Chandler SH, Aronin N, DiFiglia M, Levine MS (2005) Striatal potassium channel dysfunction in Huntington’s disease transgenic mice. J Neurophysiol 93:2565–2574

    CAS  PubMed  Google Scholar 

  • Chou SY, Lee YC, Chen HM, Chiang MC, Lai HL, Chang HH, Wu YC, Sun CN, Chien CL, Lin YS, Wang SC, Tung YY, Chang C, Chern Y (2005) CGS21680 attenuates symptoms of Huntington’s disease in a transgenic mouse model. J Neurochem 93:310–320

    CAS  PubMed  Google Scholar 

  • Gines S, Seong IS, Fossale E, Ivanova E, Trettel F, Gusella JF, Wheeler VC, Persichetti F, MacDonald ME (2003) Specific progressive cAMP reduction implicates energy deficit in presymptomatic Huntington’s disease knock-in mice. Hum Mol Genet 12:497–508

    CAS  PubMed  Google Scholar 

  • Helmlinger D, Yvert G, Picaud S, Marienne K, Sahel J, Mandel JL, Devys D (2002) Progressive retinal degeneration and dysfunction in R6 Huntington’s disease mice. Hum Mol Genet 11:3351–3359

    CAS  PubMed  Google Scholar 

  • Hickey MA, Morton AJ (2000) Mice transgenic for the Huntington’s disease mutation are resistant to chronic 3-nitropropionic acid-induced striatal toxicity. J Neurochem 75:2163–2171

    CAS  PubMed  Google Scholar 

  • Hockly E, Woodman B, Mahal A, Lewis CM, Bates G (2003a) Standardization and statistical approaches to therpeutic trials in the R6/2 mouse. Brain Res Bull 61:469–479

    PubMed  Google Scholar 

  • Hockly E, Richon VM, Woodman B, Smith D, Zhou X, Rosa E, Sathasivam K, Ghazi-Noori S, Mahal A, Lowden PAS, Steffan JS, Marsh JL, Thompson LM, Lewis CXM, Marks PA, Bates GP (2003b) Suberoylanilide hydroxamic acid, a histone deacetylase inhibitor, ameliorates motor deficits in a mouse model of Huntington’s disease. Proc Natl Acad Sci U S A 100:2041–2046

    PubMed Central  CAS  PubMed  Google Scholar 

  • Keene CD, Rodrigues CMP, Eich T, Chhabra MS, Steer CJ, Low WC (2002) Tauroursodeoxycholic acid, a bile acid, is neuroprotective in a transgenic animal model of Huntington’s disease. Proc Natl Acad Sci U S A 99:10671–10676

    PubMed Central  CAS  PubMed  Google Scholar 

  • Laforet GA, Sapp E, Chase K, McIntyre C, Boyce FM, Campbell M, Cadigan BA, Warzecki L, Tagle DA, Reddy PH, Cepeda C, Calvert CR, Jokel ES, Klapstein GJ, Ariano MA, Levine MS, DiFiglia M, Aronin N (2001) Changes in cortical and striatal neurons predict behavioral and electrophysiological abnormalities in a transgenic murine model of Huntington’s disease. J Neurosci 21:9112–9123

    CAS  PubMed  Google Scholar 

  • Lee WCM, Yoshihara M, Littleton JT (2004) Cytoplasmatic aggregates trap polyglutamine-containing proteins and block axonal transport in a Drosophila model of Huntington’s disease. Proc Natl Acad Sci U S A 101:3224–3229

    PubMed Central  CAS  PubMed  Google Scholar 

  • Ona VO, Li M, Vonsattel JPG, Andrews LJ, Khan SQ, Chung WM, Frey AS, Menon AS, Li XJ, Stieg PE, Yuan J, Penney JB, Young AB, Cha JHJ, Friedlander RM (1999) Inhibition of caspase-1 slows disease progression in a mouse model of Huntington’s disease. Nature 399:264–267

    Google Scholar 

  • Segalat L, Neri C (2003) C. elegans comme modele pour les maladies degeneratives hereditaires humaines. Med Sci 19:1218–1225

    Google Scholar 

  • Slow EJ, van Raamsdonk J, Rogers D, Coleman SH, Graham RK, Deng Y, Oh R, Bissada N, Hossain SM, Yang YZ, Li XJ, Simpson EM, Gutekunst CA, Leavitt BR, Hayden MR (2003) Selective striatal neuronal loss in a YAC128 mouse model of Huntington disease. Hum Mol Genet 12:1555–1567

    CAS  PubMed  Google Scholar 

  • Von Hörsten S, Schmitt I, Nguyen HP, Holzmann C, Schmidt T, Walther T, Bader M, Pabst R, Kobbe P, Krotova J, Stiller D, Kask A, Vaarmann A, Rathke-Hartlieb S, Schulz JB, Grasshoff U, Bauer I, Menezes AM, Vieira-Saeker AMM, Paul M, Jones L, Lindenberg KS, Landwehrmeyer B, Bauer A, Li XJ, Riess O (2003) Transgenic rat model of Huntington’s disease. Hum Mol Genet 12:617–624

    Google Scholar 

  • Zucker B, Ludin DE, Gerds TA, Lücking CH, Landwehrmeyer GB, Feuerstein TJ (2004) Gabapentin-lactam, but not gabapentin, reduces protein aggregates and improves motor performance in a transgenic mouse model of Huntington’s disease. Naunyn Schmiedebergs Arch Pharmacol 370:131–139

    CAS  PubMed  Google Scholar 

Amyotrophic Lateral Sclerosis

  • Anger WK (1991) Animal test systems to study behavioral dysfunctions of neurodegenerative disorders. Neurotoxicology 12:403–413

    CAS  PubMed  Google Scholar 

  • Kaal ECA, Dijkstra S, van Wasterlaak MGH, Joosten EAJ, Bar PR (1999) Experimental models for ALS A short review. Neurosci Res Commun 25:1–11

    Google Scholar 

  • Morrison KE (2002) Therapies in amyotrophic lateral sclerosis – beyond riluzole. Curr Opin Pharmacol 2:302–309

    CAS  PubMed  Google Scholar 

  • Rowland LP, Shneider NA (2001) Amyotrophic lateral sclerosis. N Engl J Med 344:1688–1700

    CAS  PubMed  Google Scholar 

  • Senior K (2002) New rodent models gnawing at the black box of ALS. Drug Discov Today 7:1070–1071

    PubMed  Google Scholar 

  • Waldmeier PC (2003) Prospects for antiapoptotic drug therapy in neurodegenerative diseases. Prog Neuropsychopharmacol Biol Psychiatry 27:303–321

    CAS  PubMed  Google Scholar 

Transgenic Animal Models of Amyotrophic Lateral Sclerosis

  • Amedola J, Verrier B, Roubertoux P, Durand J (2004) Altered sensorimotor development in a transgenic mouse model of amyotrophic lateral sclerosis. Eur J Neurosci 20:2822–2826

    Google Scholar 

  • Andreassen OA, Dedeoglu A, Friedlich A, Ferrante KL, Hughes DS, Szabo C, Beal MF (2001) Effects of an inhibitor of poly(ADP-riböse) polymerase, desmethylselegiline, trientine, and lipoic acid in transgenic ALS mice. Exp Neurol 168:419–424

    CAS  PubMed  Google Scholar 

  • Azari MF, Lopes EC, Stubna C, Turner BJ, Zang D, Nicola NA, Kurek JB, Cheema SS (2003) Behavioral and anatomical effects of systematically administered leukemia inhibitory factor in the SOD1G93A GIH mouse model of familial amyotrophic lateral sclerosis. Brain Res 982:92–97

    CAS  PubMed  Google Scholar 

  • Azzouz M, Hottinger A, Paterna JC, Zurn AD, Aebischer P, Büeler H (2000) Increased motoneuron survival and improved neuromuscular function in transgenic ALS mice after intraspinal injection of an adeno-associated virus encoding Bcl-2. Hum Mol Genet 9:803–811

    CAS  PubMed  Google Scholar 

  • Bordet T, Schmalbruch H, Pettmann B, Hagege A, Castelnau-Ptakhine L, Kahn A, Haase G (1999) Adenoviral cardiotrophin-1 gene transfer protects pmn mice from progressive neuronopathy. J Clin Invest 104:1077–1085

    PubMed Central  CAS  PubMed  Google Scholar 

  • Bordet T, Lesbordes JC, Rouhani S, Castelnau-Ptakhine L, Schmalbruch H, Haase G, Kahn A (2001) Protective effects of cardiotrophin-1 adenoviral gene transfer on neuromuscular degeneration in transgenic ALS mice. Hum Mol Genet 10:1925–1933

    CAS  PubMed  Google Scholar 

  • Bruijn LI, Houseweart MK, Kato S, Anderson KL, Andersson SD, Omaha E, Reaume AG, Scott RW, Cleveland DW (1998) Aggregation and motor neuron toxicity of an ALS-linked SOD1 mutant independent from wild-type SOD1. Science 281:1851–1854

    CAS  PubMed  Google Scholar 

  • Canton T, Böhme GA, Boireau A, Bordier F, Mignani S, Jimonet P, Jahn G, Alavijeh M, Stygall J, Roberts S, Brealey C, Vulhorgne M, Debono MW, le Guern S, Laville M, Briet D, Roux M, Stutzmann JM, Pratt J (2001) RPR 119990, a novel α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid antagonist: synthesis, pharmacological properties, and activity in an animal model of amyotrophic lateral sclerosis. J Pharmacol Exp Ther 299:314–322

    CAS  PubMed  Google Scholar 

  • Copray JCVM, Jaarsma D, Küst BM, Bruggeman RWG, Mantingh I, Brouwer N, Boddek HWGM (2003) Expression of the low affinity neurotropin receptor p75 in spinal motoneurons in a transgenic mouse model for amyotrophic lateral sclerosis. Neuroscience 116:685–694

    CAS  PubMed  Google Scholar 

  • Doble A (1996) The pharmacology and mechanism of action of riluzole. Neurology 466(Suppl 4):S233–S241

    Google Scholar 

  • Farah CA, Nguyen MD, Julien CP, Leclerc N (2003) Altered levels and distribution of microtubule-associated proteins before disease onset in a mouse model of amyotrophic lateral sclerosis. J Neurochem 84:77–86

    CAS  PubMed  Google Scholar 

  • Gurney ME, Pu H, Chiu AY, dal Canto MC, Polchow CY, Alexander DD, Caliendo J, Hentati A, Known YW, Deng HX (1994) Motor neuron degeneration in mice that express a human Cu, Zn superoxide dismutase mutation. Science 264:1772–1775

    CAS  PubMed  Google Scholar 

  • Gurney ME, Fleck TJ, Himes CS, Hall ED (1998) Riluzole preserves motor function in a transgenic model of familial amyotrophic lateral sclerosis. Neurology 50:62–66

    CAS  PubMed  Google Scholar 

  • Haase G, Pettmann B, Vigne E, Castelnau-Ptakhine L, Schmalbruch H, Kahn A (1998) Adenovirus-mediated transfer of the neurotrophin-3 gene into skeletal muscle of pmn mice: therapeutic effects and mechanism of action. J Neurol Sci 160(Suppl 1):S97–S105

    CAS  PubMed  Google Scholar 

  • Howland DS, Liu J, She Y, Goad B, Maragakis NJ, Kim B, Erickson J, Kulik J, DeVito L, Psaltis G, DeGennaro LJ, Cleveland DW, Rothstein JD (2002) Focal loss of the glutamate transporter EAAT2 in a transgenic rat model of SOD1 mutant-mediated amyotrophic lateral sclerosis (ALS). Proc Natl Acad Sci U S A 99:1604–1609

    PubMed Central  CAS  PubMed  Google Scholar 

  • Jimonet P, Audiau F, Barreau M, Blanchard JC, Boireau A, Bour Y, Coleno MA, Doble A, Doerfliner G, Huu CD, Donat MH, Duchesne JM, Ganil P, Gueremy C, Honor E, Just P, Kerphirique R, Gontier S, Huberet P, Laduron PM, Le-Blevec J, Meunier M, Miquet JM, Nemecek C, Mignani S (1999) Riluzole series. Synthesis and in vivo “antiglutamate” activity of 6-substituted-2-benzothiazolamines and 3-substituted-2-imino-benzothiazolines. J Med Chem 42:2828–2843

    CAS  PubMed  Google Scholar 

  • Jung C, Rong Y, Doctrow S, Baudry M, Malfroy B, Xu Z (2001) Synthetic superoxide dismutase/catalase mimetics reduce oxidative stress and prolong survival in a mouse amyotrophic lateral sclerosis model. Neurosci Lett 304:157–160

    CAS  PubMed  Google Scholar 

  • Kostic V, Jackson-Lewis V, de Bilbao F, Dubois-Dauphin M, Przedborski S (1997) Bcl-2: prolonging life in a transgenic mouse model of familial amyotrophic lateral sclerosis. Science 2277:559–562

    Google Scholar 

  • Lee M, Hyun DH, Halliwell B, Jenner P (2001) Effect of overexpression of wild-type and mutant Cu/ZN-superoxide dismutases on oxidative stress and cell death induced by hydrogen peroxide, 4-hydroxynonenal or serum deprivation: potentiation of injury by ALS-related mutant superoxide dismutases and protection by Bcl-2. J Neurochem 78:209–220

    CAS  PubMed  Google Scholar 

  • Li M, Ona VO, Guégan C, Chen M, Jackson-Lewis V, Andrews LJ, Olszewski AJ, Stieg PE, Lee JP, Przedborski S, Friedlander RM (2000) Functional role of caspase-1 and caspase-3 in an ALS transgenic mouse model. Science 288:335–339

    CAS  PubMed  Google Scholar 

  • Maragakis NJ, Jackson M, Ganel R, Rothstein JD (2003) Topiramate protects against motor neuron degeneration in organotypic spinal cord cultures but not in G93A SOD1 transgenic mice. Neurosci Lett 338:107–110

    CAS  PubMed  Google Scholar 

  • Nagai M, Aoki M, Miyoshi I, Kato M, Pasinelli P, Kasai N, Brown RH Jr, Itoyama Y (2001) Rats expressing human cytosolic copper-zinc superoxide dismutase transgenes with amyotrophic lateral sclerosis: associated mutations develop motor neuron diseases. J Neurosci 21:9246–9254

    CAS  PubMed  Google Scholar 

  • Nguyen MD, Lariviere RC, Julien JP (2001) Deregulation of Cdk5 in a mouse model of ALS: toxicity alleviated by perikaryal neurofilament inclusions. Neuron 30:135–147

    CAS  PubMed  Google Scholar 

  • Pasinelli P, Borchelt DR, Houseweart MK, Cleveland DW, Brown HR Jr (1998) Caspase-1 is activated in neural cells and tissue with amyotrophic lateral sclerosis-associated mutations in copper-zinc dismutase. Proc Natl Acad Sci U S A 95:15763–15768

    PubMed Central  CAS  PubMed  Google Scholar 

  • Raiteri L, Stigliani S, Zappettini S, Mercuri NB, Raiteri M, Bonanno G (2004) Excessive and precocious glutamate release in a mouse model of amyotrophic lateral sclerosis. Neuropharmacology 46:782–792

    CAS  PubMed  Google Scholar 

  • Ralph GS, Radcliffe PA, Day DM, Carthy JM, Leroux MA, Lee DCP, Wong LF, Bilsland LG, Greensmith L, Kingsman SM, Mitrophanous KA, Mazarakis ND, Azzouz M (2005a) Silencing mutant SOD1 using RNAi protects against neurodegeneration and extends survival in an ALS model. Nat Med 11:429–433

    CAS  PubMed  Google Scholar 

  • Ralph GS, Mazarakis ND, Azzouz M (2005b) Therapeutic gene silencing in neurological disorders, using interfering RNA. J Mol Med 83:413–419

    CAS  PubMed  Google Scholar 

  • Raman C, McAllister SD, Rizvi G, Patel SG, Moore DH, Abood ME (2004) Amyotrophic lateral sclerosis: delayed disease progression in mice by treatment with a cannabinoid. Amyotroph Lateral Scler Other Motor Neuron Disord 5:33–39

    CAS  PubMed  Google Scholar 

  • Robertson J, Doroudchi MM, Nguyen MD, Durham HD, Strong MJ, Shaw G, Julien JP, Mushynski WE (2003) A neurotoxic peripherin splice variant in a mouse model of ALS. J Cell Biol 160:939–949

    PubMed Central  CAS  PubMed  Google Scholar 

  • Schmalbruch H, Jensen HJ, Bjaerg M, Kamieniecka Z, Kurland R (1991) A new mouse mutant with progressive motor neuropathy. J Neuropathol Exp Neurol 50:192–204

    CAS  PubMed  Google Scholar 

  • Snow RJ, Turnbull J, da Silva S, Jinang F, Tzarnopolsky MA (2003) Creatine supplementation and riluzole treatment provide similar beneficial effects in copper, zinc superoxide dismutase (G93A) transgenic mice. Neuroscience 119:661–667

    CAS  PubMed  Google Scholar 

  • Spooren WP, Hengerer B (2000) DNA laddering and caspase 3-like activity in the spinal cord of a mouse model of familial amyotrophic lateral sclerosis. Cell Mol Biol 46:63–69

    CAS  PubMed  Google Scholar 

  • Trieu VN, Uckun FM (1999) Genistein is neuroprotective in murine models of female amyotrophic lateral sclerosis and stroke. Biochem Biophys Res Commun 258:685–688

    CAS  PubMed  Google Scholar 

  • Van Damme P, Leyssen M, Callewaen G, Robberecht W, van den Bosch L (2003) The AMPA receptor antagonist NBQX prolongs survival in a transgenic mouse model of amyotrophic lateral sclerosis. Neurosci Lett 343:81–84

    PubMed  Google Scholar 

  • Vukosavic S, Dubois-Dauphin M, Romero N, Przedborski S (1999) Bax and Bcl-2 interaction in a transgenic mouse model of familial amyotrophic lateral sclerosis. J Neurochem 73:2460–2468

    CAS  PubMed  Google Scholar 

  • Vukosavic S, Stefanis L, Jackson-Lewis V, Guégan C, Romero N, Chen C, Dubois-Dauphin M, Przedborski S (2000) Delaying caspase activation by Bcl-2: a clue to disease retardation in a transgenic mouse model of amyotrophic lateral sclerosis. J Neurosci 20:9119–9125

    CAS  PubMed  Google Scholar 

  • Waibel S, Reuter A, Malessa S, Blaugrund E, Ludolph AG (2004) Rasagiline alone and in combination with riluzole prolongs survival in an ALS mouse model. J Neurol 251:1080–1084

    CAS  PubMed  Google Scholar 

  • Wendt S, Dedeoglu A, Speer O, Wallimann T, Beal MF, Andreassen OA (2002) Reduced creatine kinase activity in transgenic amyotrophic lateral sclerosis mice. Free Radic Biol Med 32:920–926

    CAS  PubMed  Google Scholar 

  • Zhu S, Stavrovskaya IG, Drozda M, Kim BYS, Ona V, Li M, Sarang S, Liu AS, Hartley DM, Wu DC, Gullans S, Ferrante RJ, Przedborski S, Kristal BS, Friedlander RM (2002) Minocycline inhibits cytochrome c release and delays progression of amyotrophic lateral sclerosis in mice. Nature 417:74–78

    CAS  PubMed  Google Scholar 

Spinal Muscular Atrophy

  • Frugier T, Nicole S, Cifuentes-Diaz C, Melki J (2002) The molecular bases of spinal muscular atrophy. Curr Opin Genet Dev 12:294–298

    CAS  PubMed  Google Scholar 

  • Iannnaccone ST, Smith SA, Simard LR (2004) Spinal muscular atrophy. Curr Neurol Neurosci Rep 4:74–80

    Google Scholar 

  • Nicole S, Diaz CC, Frugier T, Melki J (2002) Spinal muscular atrophy: recent advances and future perspectives. Muscle Nerve 26:4–13

    CAS  PubMed  Google Scholar 

  • Ogino S, Wilson RB (2004) Spinal muscular atrophy: molecular genetics and diagnostics. Expert Rev Mol Diagn 4:15–29

    CAS  PubMed  Google Scholar 

  • Schara U, Mortier W (2004) Neuromuskuläre Erkrankungen. Teil 1: Spinale Muskelatrophien, periphere Nervenerkrankungen, kongenitale myasthenische Syndrome. Nervenarzt 75:1231–1245

    CAS  PubMed  Google Scholar 

  • Strober JB, Tennekoon GI (1999) Progressive spinal muscular atrophies. J Child Neurol 14:691–695

    CAS  PubMed  Google Scholar 

  • Talbot K, Davies KE (2001) Spinal muscular atrophy. Semin Neurol 21:189–197

    CAS  PubMed  Google Scholar 

  • Wirth B (2002) Spinal muscular atrophy: state-of-the-art and therapeutic perspectives. Amyotroph Lateral Scler Other Motor Neuron Disord 3:87–95

    CAS  PubMed  Google Scholar 

Transgenic Animal Models of Spinal Muscular Atrophy

  • Andreassi C, Jarecki J, Zhou J, Coovert DD, Monani UR, Chen X, Whitney M, Pollok B, Zhang M, Androphy E, Burghes AHM (2001) Aclarubicin treatment restored SMH levels to cells derived from type I spinal muscular atrophy patients. Hum Mol Genet 10:2841–2849

    CAS  PubMed  Google Scholar 

  • Azzouz M, Le T, Ralph S, Walmsley L, Monani UR, Lee DCP, Wilkes F, Mitrophanous KA, Kinsman SM, Burghes AHM, Mazarakis ND (2004) Lentivector-mediated SMN replacement in a mouse model of spinal muscular atrophy. J Clin Invest 114:1726–1731

    PubMed Central  CAS  PubMed  Google Scholar 

  • Bergin A, Kim G, Price DL, Sisodia SS, Lee MK, Rabin BA (1997) Identification and characterization of a mouse homologue of spinal muscular atrophy-determining gene, survival motor neuron. Gene 204:47–53

    CAS  PubMed  Google Scholar 

  • Chang JG, Hsieh-Li HM, Jong YJ, Wang NM, Tsai CH, Li H (2001) Treatment of spinal muscular atrophy by sodium butyrate. Proc Natl Acad Sci U S A 98:9808–9813

    PubMed Central  CAS  PubMed  Google Scholar 

  • Cifuentes-Diaz C, Frugier T, Tiziano FD, Lacène E, Roblot N, Joshi V, Moreau MH, Melki J (2001) Deletion of murine SMN exon 7 directed to skeletal muscle leads to severe muscular dystrophy. J Cell Biol 152:1107–1114

    PubMed Central  CAS  PubMed  Google Scholar 

  • Cifuentes-Diaz C, Nicole S, Velasco ME, Borra-Cebrian C, Panozzo C, Frugier T, Millet G, Roblot N, Joshi V, Melki J (2002) Neurofilament accumulation at the motor endplate and lack of axonal sprouting in the spinal muscular atrophy model. Hum Mol Genet 11:1439–1447

    CAS  PubMed  Google Scholar 

  • Deniselle MCG, González S, Piroli G, Ferrini M, Lima AE, de Nicola AF (1997) Glucocorticoid receptors and actions in the spinal cord of the Wobbler mouse, a model of neurodegenerative diseases. J Steroid Biochem Mol Biol 60:205–213

    Google Scholar 

  • DiDonato CJ, Chen XN, Noya D, Korenberg JR, Nadeau JH, Simard LR (1997) Cloning, characterization, and copy number of the murine survival motor neuron gene: homolog of the spinal muscular atrophy-determining gene. Genome Res 7:339–352

    CAS  PubMed  Google Scholar 

  • DiDonato C, Lorson CL, de Repentigny Y, Simard L, Chartrand C, Androphy EJ, Kothary R (2001) Regulation of murine survival motor neuron (Smn) protein levels by modifying Smn exon 7 splicing. Hum Mol Genet 10:2727–2736

    CAS  PubMed  Google Scholar 

  • Ferri A, Sanes JR, Coleman MP, Cunningham JM, Kato AC (2003) Inhibiting axon degeneration and synapse loss attenuates apoptosis and disease progression in a mouse model of motoneuron disease. Curr Biol 13:669–673

    CAS  PubMed  Google Scholar 

  • Ferri A, Melki J, Kato AC (2004) Progressive and selective degeneration of motoneurons in a model of SMA. Neuroreport 15:275–280

    CAS  PubMed  Google Scholar 

  • Fricker J (2000) Mouse model of spinal muscular atrophy. Drug Discov Today 5:220–221

    PubMed  Google Scholar 

  • Frugier T, Tiziano FD, Cifuentes-Diaz C, Miniou P, Roblot N, Dierich A, le Meur M, Melki J (2000) Nuclear targeting defect of SMN lacking the C-terminus in a mouse model of spinal muscular atrophy. Hum Mol Genet 9:849–858

    CAS  PubMed  Google Scholar 

  • Grohmann K, Rossoll W, Kobsar I, Holtmann B, Jablonka S, Wessig C, Stoltenburg-Didinger G, Fischer U, Hübner C, Martini R, Sendtner M (2004) Characterization of Ighmbp2 in motor neurons and implications for the pathomechanism in a mouse model of human spinal muscular atrophy with respiratory distress type I (SMARD1). Hum Mol Genet 13:2031–2042

    CAS  PubMed  Google Scholar 

  • Haddad H, Cifuentes-Diaz C, Miroglio A, Roblot N, Joshi V, Melki J (2003) Riluzole attenuates spinal muscular atrophy disease progression in a mouse model. Muscle Nerve 28:432–437

    CAS  PubMed  Google Scholar 

  • He Q, Lowrie C, Shelton GD, Castellani RJ, Menotti-Raymond M, Murphy W, O’Brien SJ, Swanson WF, Fyfe JC (2005) Inherited motor neuron disease in domestic cats: a model of spinal muscular atrophy. Pediatr Res 57:324–330

    PubMed  Google Scholar 

  • Hsieh-Li JHM, Chang JG, Jong YJ, Wu MH, Wang NM, Tsai CH, Li H (2000) A mouse model for spinal muscular atrophy. Nat Genet 24:66–69

    CAS  PubMed  Google Scholar 

  • Jablonka S, Schrank B, Kralewski M, Rossoll W, Sendtner M (2000) Reduced survival motor neuron (Smn) gene dose in mice leads to motor neuron degeneration: an animal model for spinal muscular atrophy type III. Hum Mol Genet 9:341–346

    CAS  PubMed  Google Scholar 

  • Jablonka S, Bandilla M, Wiese S, Bühler D, Wirth B, Sendtner M, Fischer U (2001) Co-regulation of survival of motor neuron (SMN) protein and its interactor SIP1 during development and in spinal muscular atrophy. Hum Mol Genet 10:497–505

    CAS  PubMed  Google Scholar 

  • Jong YJ, Chang JG, Lin SP, Yang TY, Wang JC, Chang CP, Lee CC, Li H, Hsieh-Li HM, Tsai CH (2000) Analysis of the mRNA transcripts of the survival motor neuron (SMN) gene in the tissue of an SMA fetus and the peripheral blood mononuclear cells of normal carriers and SMA patients. J Neurol Sci 173:147–153

    CAS  PubMed  Google Scholar 

  • Le TT, Pham LT, Butchbach ME, Zhang HL, Monani UR, Coovert DD, Gavrilina TO, Xing L, Bassell GJ, Burghes AH (2005) SMNDelta7, the major product of the centromeric survival motor neuron (SMN2) gene, extends survival in mice with spinal muscular atrophy and associates with full-length SMN. Hum Mol Genet 14:845–857

    CAS  PubMed  Google Scholar 

  • Lesbordes JC, Cifuentes-Diaz C, Miroglio A, Joshi V, Bordet T, Melki J (2003) Therapeutic benefits of cardiotrophin1 gene transfer in a mouse model of spinal molecular atrophy. Hum Mol Genet 12:1233–1239

    CAS  PubMed  Google Scholar 

  • Melki J (2001) Mouse models of spinal muscular atrophy. Acta Myologica 20:159–161

    Google Scholar 

  • Monani UR, Sendtner M, Coovert DD, Parsons DW, Andeasst C, Le TT, Jablonka S, Schrank B, Rossol W, Prior TW, Morris GE, Burghes AHM (2000a) The human centromeric survival motor neuron gene (SMN2) rescues embryonic lethality in Smn(-1-) mice and results in a mouse with spinal muscular atrophy. Hum Mol Genet 9:333–339

    CAS  PubMed  Google Scholar 

  • Monani UR, Coovert DD, Burghes AHM (2000b) Animal models of spinal muscular atrophy. Hum Mol Genet 9:2451–2457

    CAS  PubMed  Google Scholar 

  • Monani UR et al (2003) A transgene carrying an A2G missense mutation in the SMN gene modulates phenotypic severity in mice with severe (type I) spinal muscular atrophy. J Cell Biol 160:41–52

    PubMed Central  CAS  PubMed  Google Scholar 

  • Rossoll W, Jablonka S, Andreassi C, Kröning AK, Karle K, Monani UR, Sendtner M (2003) SMN, the spinal muscular atrophy-determining gene product, modulátes axon growth and location of β-actin mRNA in growth cones of motoneurons. J Cell Biol 163:801–812

    PubMed Central  CAS  PubMed  Google Scholar 

  • Schrank B, Götz R, Gunnersen J, Ure JM, Toyka KV, Smith AG, Sendtner M (1997) Inactivation of the survival motor gene, a candidate gene for human spinal muscular atrophy, leads to massive cell death in early mouse embryos. Proc Natl Acad Sci U S A 94:9920–9925

    PubMed Central  CAS  PubMed  Google Scholar 

  • Tucker KE, Berciano MT, Jacobs EY, LePage DF, Shpargel KB, Rossire JJ, Chan EKL, Lafarga M, Conlon RA, Matera AG (2001) Residual Cajal bodies in coilin knockout mice fail to recruit SM snRNPs and SMN, the spinal muscular atrophy gene product. J Cell Biol 154:293–307

    PubMed Central  CAS  PubMed  Google Scholar 

Spinal and Bulbar Muscular Atrophy

  • Katsuno M, Adachi H, Inukai A, Subue G (2003) Transgenic mouse models of spinal and bulbar muscular atrophy (SBMA). Cytogenet Genome Res 100:243–251

    Google Scholar 

  • Katsuno M, Adachi H, Tnaka F, Sobue G (2004) Spinal and bulbar muscular atrophy: ligand-dependent pathogenesis and therapeutic perspectives. J Mol Med 82:298–307

    CAS  PubMed  Google Scholar 

Transgenic Animal Models of Spinal and Bulbar Muscular Atrophy

  • Abel A, Walcott J, Woods JA, Duda J, Merry DE (2001) Expression of expandet repeat androgen receptor produces neurological disease in transgenic mice. Hum Mol Genet 10:107–116

    CAS  PubMed  Google Scholar 

  • Adachi H, Kume A, Li M, Nakagomi Y, Niwa H, Do J, Sang C, Kobayashi Y, Doyu M, Sobue G (2001) Transgenic mice with an expanded CAG repeat controlled by the human AR promotor show polyglutamine nuclear inclusions and neuronal dysfunction without neuronal cell death. Hum Mol Genet 10:1039–1048

    CAS  PubMed  Google Scholar 

  • Adachi H, Katsuno M, Minamiyama M, Sang C, Pagoulatos G, Angelidis C, Kusakabe M, Yoshiki A, Kobayashi Y, Duyu M, Sobue G (2003) Heat shock protein 70 chaperone overexpression ameliorates phenotypes of the spinal and bulbar muscular transgenic mouse model by reducing nuclear localized mutant androgen receptor protein. J Neurosci 23:2203–2211

    CAS  PubMed  Google Scholar 

  • Bates GP, Davies SW (1997) Transgenic mouse models of neurodegenerative disease caused by CAG/polyglutamine expansions. Mol Med Today 3:508–515

    CAS  PubMed  Google Scholar 

  • Chevalier-Larsen ES, O’Brien CJ, Wang H, Jenkins SC, Holder L, Lieberman AP, Merry DE (2004) Castration restores function and neurofilament alterations of aged symptomatic males in a transgenic mouse model of spinal and bulbar muscular atrophy. J Neurosci 24:4778–4786

    CAS  PubMed  Google Scholar 

  • Holmberg M, Duyckaerts C, Durr A, Cancel G, Gourfinkel-An I, Damier P, Faucheux B, Trottier Y, Hirsch EC, Agid Y, Brice A (1998) Spinocerebellar ataxia type 7 (SCAT7): a neurodegenerative disorder with neuronal intranuclear inclusions. Hum Mol Genet 7:913–918

    CAS  PubMed  Google Scholar 

  • Katsuno M, Adachi H, Kume A, Li M, Nakagomi Y, Niwa H, Sang C, Kobayashi Y, Doyu M, Subue G (2002) Testosterone reduction prevents phenotypic expression in a transgenic mouse model of spinal and bulbar muscular atrophy. Neuron 35:843–854

    CAS  PubMed  Google Scholar 

  • Katsuno M, Adachi H, Doyu M, Minamiyama M, Sang C, Kobayashi Y, Inukai A, Sobue G (2003) Leuprolin rescues polyglutamine-dependent phenotypes in a transgenic mouse model of spinal and bulbar muscular atrophy. Nat Med 9:768–773

    Google Scholar 

  • Kobayashi Y, Miwa S, Merry DE, Kume A, Mei L, Doyu M, Sobue G (1998) Caspase-3 cleaves the expanded androgen receptor protein of spinal and bulbar muscular atrophy in a polyglutamine repeat length-dependent manner. Biochem Biophys Res Commun 252:145–150

    CAS  PubMed  Google Scholar 

  • MacManamny P, Chy HS, Finkelstein DI, Craithorn RG, Crack PJ, Kola I, Cheema SS, Horne MK, Wreford NG, O’Bryan MK, de Ketser DM, Morrison JR (2002) A mouse model of spinal and bulbar muscular atrophy. Hum Mol Genet 11:2103–2111

    Google Scholar 

  • Minamiyama M, Katsuno M, Adachi H, Waza M, Sang C, Kobayashi Y, Tanaka F, Doyu M, Inukai A, Subue G (2004) Sodium butyrate ameliorates phenotypic expression in a transgenic mouse model of spinal and bulbar muscular atrophy. Hum Mol Genet 13:1183–1192

    CAS  PubMed  Google Scholar 

  • Niwa H, Yamamura K, Miyazaki J (1991) Efficient selection of high-expression transfectants with a novel eukaryotic vector. Gene 108:193–199

    CAS  PubMed  Google Scholar 

  • Walcott JL, Merry DE (2002) Trinucleotide repeat disease: the androgen receptor in spinal and bulbar muscular atrophy. Vit Horm 65:127–147

    CAS  Google Scholar 

Models of Down Syndrome

  • Bimonte-Nelson H, Hunter CL, Nelson ME, Granholm ACE (2003) Frontal cortex BDNF levels correlate with working memory in an animal model of Down syndrome. Behav Brain Res 139:47–57

    CAS  PubMed  Google Scholar 

  • Borella A, Sumangali R, Ko J, Whitaker-Azmitia PM (2003) Characterization of social behaviors and oxytoninergic neurons in the S-100β overexpressing mouse model of Down syndrome. Behav Brain Res 141:229–236

    CAS  PubMed  Google Scholar 

  • Cardenas AM, Allen DD, Arriagada C, Olivares A, Bennett LB, Caviedes R, Dagnino-Subriabre A, Mendoza IE, Segura-Aguilar J, Rapoport SI, Caviedes P (2002) Establishment and characterization of immortal neuronal cell lines derived from the spinal cord of normal and trisomy 16 fetal mice, an animal model of Down syndrome. J Neurosci Res 68:46–58

    CAS  PubMed  Google Scholar 

  • Cooper JD, Salehi A, Delcroix JD, Howe CL, Belichenko PV, Chua-Couzens J, Kilbridge JF, Carison EJ, Epstein CJ, Mobley WC (2001) Failed retrograde transport of NGF in a mouse model of Down’s syndrome: reversal of cholinergic neurodegenerative phenotypes following NGF infusion. Proc Natl Acad Sci U S A 98:10439–10444

    PubMed Central  CAS  PubMed  Google Scholar 

  • Costa ACS, Walsh K, Davisson MT (1999) Motor dysfunction in a mouse model for Down syndrome. Physiol Behav 68:211–220

    CAS  PubMed  Google Scholar 

  • Coussons-Read ME, Crnic LS (1996) Behavioral assessment of the Ts65Dn mouse, a model for Down syndrome: altered behavior in the elevated plus maze and open field. Behav Genet 26:7–13

    CAS  PubMed  Google Scholar 

  • Cox DR, Smith SA, Epstein LB, Epstein CJ (1984) Mouse trisomy 16 as a model of human trisomy 21 (Down syndrome): production of a viable trisomy 16 diploid mouse chimera. Dev Biol 101:416–424

    CAS  PubMed  Google Scholar 

  • Davisson MT, Schmidt C, Reeves RH, Irving NG, Akeson EC, Harris BS, Bronson RT (1993) Segmental trisomy as a mouse model for Down syndrome. Prog Clin Biol Res 384:117–133

    CAS  PubMed  Google Scholar 

  • Ema M, Ikegami S, Hosoya T, Mimura J, Ohtani H, Nakao K, Inokuchi K, Katsuki M, Fujii-Kuriyama Y (1999) Mild impairment of learning and memory in mice overexpressing the mSim2 gene located on chromosome 16: an animal model of Down’s syndrome. Hum Mol Genet 8:1409–1415

    CAS  PubMed  Google Scholar 

  • Epstein CJ, Cox DR, Epstein LB (1985) Mouse trisomy 16: an animal model for human trisomy 21 (Down syndrome). Ann N Y Acad Sci 450:157–168

    CAS  PubMed  Google Scholar 

  • Friend WC, Clapoff S, Landry C, Becker LE, O’Hanlon D, Allore RJ (1992) Cell-specific expression of high levels of human S100 beta in transgenic mouse brain is dependent on gene dosage. J Neurosci 12:4337–4346

    CAS  PubMed  Google Scholar 

  • Galdzicki Z, Siarey R, Pearce R, Stoll J, Rapoport SI (2001) On the cause of mental retardation in Down syndrome: extrapolation from full and segmental trisomy 16 mouse models. Brain Res Rev 35:115–145

    CAS  PubMed  Google Scholar 

  • Granholm ACE, Ford KA, Hyde LA, Bimonta HA, Hunter CL, Nelson M, Albeck D, Sanders LA, Mufson EJ, Cmic LS (2002) Estrogen restores cognition and cholinergic phenotype in an animal model of Down syndrome. Physiol Behav 77:371–385

    CAS  PubMed  Google Scholar 

  • Holtzman DM, Bayney RM, Li Y, Khosrovi H, Berger CN, Epstein CJ, Mobley MC (1992) Dysregulation of gene expression in mouse trisomy 16, an animal model of Down syndrome. EMBO J 11:619–627

    PubMed Central  CAS  PubMed  Google Scholar 

  • Klein SL, Kriegsfeld LJ, Hairston JE, Rau V, Nelson RJ, Yarowsky PJ (1996) Characterization of sensomotor performance, reproductive and aggressive behaviors in segmental trisomic 16 (Ts65Dn) mice. Physiol Behav 60:1159–1164

    CAS  PubMed  Google Scholar 

  • Kola I, Hertzog PJ (1997) Animal models in the study of the biological function of human chromosome 21 and their role in the pathology of Down syndrome. Hum Mol Genet 6:1713–1727

    CAS  PubMed  Google Scholar 

  • Moran TH, Capone GT, Knipp S, Davisson MT, Reeves RH, Gearhart JD (2002) The effects of piracetam on cognitive performance in a mouse model of Down’s syndrome. Physiol Behav 77:403–409

    CAS  PubMed  Google Scholar 

  • Shetty HU, Holloway HW, Acevedo LD, Galdzicki Z (1996) Brain accumulation of myo-inositol in the trisomy 16 mouse, an animal model of Downs’s syndrome. Biochem J 313(pt 1):31–33

    PubMed Central  CAS  PubMed  Google Scholar 

  • Stasko MR, Costa AC (2004) Experimental parameters affecting the Morris water maze performance of a mouse model of Down syndrome. Behav Brain Res 154:1–17

    PubMed  Google Scholar 

  • Sweeney JE, Hohmann CF, Oster-Granite ML, Coyle JT (1989) Neurogenesis of the basal forebrain in euploid and trisomy 16 mice: an animal model for developmental disorders in Down syndrome. Neuroscience 31:413–425

    CAS  PubMed  Google Scholar 

Models of Wilson’s Disease

  • Adachi Y, Okyama Y, Miya H, Toshinori K (1997) Presence of ATP-dependent copper transport in the hepatocyte canalicular membrane of the Long-Evans Cinnamon rat, an animal of Wilson disease. J Hepatol 26:216–217

    CAS  PubMed  Google Scholar 

  • Brewer GJ, Hedera P, Kluin KJ, Carlson M, Askari F, Dick RB, Sitterly J, Fink JK (2003) Treatment of Wilson disease with ammonium tetrathiomolybdate: III. Initial therapy in a total of 55 neurologically affected patients and follow-up with zinc therapy. Arch Neurol 60:379–385

    PubMed  Google Scholar 

  • Grimes A, Hearn CJ, Lockhart P, Newgreen DF, Mercer JFB (1997) Molecular basis of the brindled mouse mutant (Mo br): a murine model of Menkes disease. Hum Mol Genet 6:1037–1042

    CAS  PubMed  Google Scholar 

  • Klein D, Lichtmannegger J, Heinzmann U, Müller-Höcker J, Micaelsen S, Summer KH (1998) Association of copper to metallothionein in hepatic lysosomes of Long-Evans cinnamon (LEC) rats during the development of hepatitis. Eur J Clin Invest 28:302–310

    CAS  PubMed  Google Scholar 

  • Klein D, Lichtmannegger J, Heinzmann U, Summer KH (2000) Dissolution of copper-rich granules in hepatic lysosomes by d-penicillamine prevents the development of fulminant hepatitis in Long-Evans cinnamon rats. J Hepatol 32:193–201

    CAS  PubMed  Google Scholar 

  • Klein D, Arora U, Lichtmannegger J, Finckh M, Heinzann U, Summer KH (2004) Tetrathiomolybdate in the treatment of acute hepatitis in an animal model of Wilson disease. J Hepatol 40:409–416

    CAS  PubMed  Google Scholar 

  • Kodama H, Murata Y (1999) Molecular genetics and pathophysiology of Menkes disease. Pediatr Int 41:430–435

    CAS  PubMed  Google Scholar 

  • Kodama H, Murata Y, Mochizuki D, Abe T (1998) Copper and ceruloplasmin metabolism in the LEC rat, an animal model of Wilson disease. J Inherit Metab Dis 21:203–206

    CAS  PubMed  Google Scholar 

  • Komatsu Y, Sadakata I, Ogra Y, Suzuki KT (2000) Excretion of copper complexed with thiomolybdate into the bile and blood in LEC rats. Chem Biol Interact 124:217–231

    CAS  PubMed  Google Scholar 

  • Komatsu Y, Ogra Y, Suzuki KT (2002) Copper balance and ceruloplasmin in chronic hepatitis in a Wilson disease animal model, LEC rats. Arch Toxicol 76:502–508

    CAS  PubMed  Google Scholar 

  • La Fontaine S, Theophilos MB, Firth SD, Gould R, Parton RG, Mercer JFB (2001) Effect of the toxic milk mutation (tx) on the function and intracellular location of Mnd, the murine homologue of the Wilson copper ATPase. Hum Mol Genet 10:361–370

    PubMed  Google Scholar 

  • Meng Y, Miyoshi I, Hirabayashi M, Su M, Mototani Y, Okamura T, Terada K, Ueda M, Enomoto K, Sugiyama T, Kasai N (2004) Restoration of copper metabolism and rescue of hepatic abnormalities in LEC rats, an animal model of Wilson disease, by expression of human ATP7B gene. Biochim Biophys Acta 1690:208–219

    CAS  PubMed  Google Scholar 

  • Murata Y, Kodama H, Abe T, Ishida N, Nishimura M, Levinson B, Gitschier J, Packman S (1997) Mutation analysis and expression of the mottled gene in the macular mouse model of Menkes disease. Pediatr Res 42:436–442

    CAS  PubMed  Google Scholar 

  • Murata Y, Kodama H, Mori Y, Kobayashi M, Abe T (1998) Mottled gene expression and copper distribution in the macular mouse, an animal model for Menkes disease. J Inherit Metab Dis 21:199–202

    CAS  PubMed  Google Scholar 

  • Nagano K, Nakamura K, Urakami KI, Umeyama K, Uchiyama H, Koiwai K, Hattori S, Yamamoto T, Matsuda I, Endo F (1998) Intracellular distribution of the Wilson’s disease gene product (ATPase7B) after in vitro and in vivo exogenous expression in hepatocytes from the LEC rat, an animal model of Wilson’s disease. Hepatology 27:799–807

    CAS  PubMed  Google Scholar 

  • Nomiyama K, Nomiyama H, Kameda N, Tsuji A, Sakuari H (1999) Mechanism of hepatorenal syndrome in rats of Long-Evans cinnamon strain, an animal model of fulminant Wilson’s disease. Toxicology 132:201–214

    CAS  PubMed  Google Scholar 

  • Palida FA, Ettinger MJ (1991) Identification of proteins involved in intracellular copper metabolism. J Biol Chem 266:4586–4592

    CAS  PubMed  Google Scholar 

  • Rossi L, de Martino A, Marchese E, Piccirilli S, Rotilio G, Ciriolo MR (2001) Neurodegeneration in the animal model of Menkes’ disease involves Bcl-2-linked apoptosis. Neuroscience 103:181–188

    CAS  PubMed  Google Scholar 

  • Silva EES, Sarles J, Buts JP, Sokal EM (1996) Successful treatment of severely decompensated Wilson disease. J Pediatr 128:285–287

    Google Scholar 

  • Stremmel W, Meyerrose KW, Niederau C, Hefter H, Kreuzpainter G, Strohmeyer G (1991) Wilson disease: clinical presentation, treatment, and survival. Ann Intern Med 115:720–726

    CAS  PubMed  Google Scholar 

  • Suzuki KT (1995) Disordered copper metabolism in LEC rats, an animal model or Wilson disease. Role of metallothionein. Res Commun Mol Pathol Pharmacol 89:221–240

    CAS  PubMed  Google Scholar 

  • Suzuki-Kurasaki M, Okabe M, Kurasaki M (1997) Copper-metallothionein in the kidney of macular mice: a model for Menkes disease. J Histochem Cytochem 45:1493–1501

    CAS  PubMed  Google Scholar 

  • Tanaka K, Kobayashi K, Fujita Y, Fukuhara C, Onosaka S, Min K (1990) Effects of chelators on copper therapy of macular mouse, a model of Menkes’ kinky disease. Res Commun Chem Pathol Pharmacol 69:217–227

    CAS  PubMed  Google Scholar 

  • Terada K, Sugiyama T (1999) The Long-Evans Cinnamon rat. An animal model for Wilson’s disease. Pediatr Int 41:414–418

    CAS  PubMed  Google Scholar 

  • Tumer Z, Moller LB, Horn N (1999) Mutation spectrum of ATP7A, the gene defective in Menkes disease. Adv Exp Med Biol 448:83–95

    CAS  PubMed  Google Scholar 

  • Yamaguchi Y, Heiny ME, Shimizu N, Aoki T, Gitlin JD (1994) Expression of the Wilson disease gene is deficient in the Long-Evans Cinnamon rat. Biochem J 301(Pt 1):1–4

    PubMed Central  CAS  PubMed  Google Scholar 

Models of Cerebellar Ataxia

  • Clark BR, LaRegina M, Tolbert DL (2000) X-linked transmission of the shaker mutation in rats with hereditary Purkinje cell degeneration and ataxia. Brain Res 858:264–273

    CAS  PubMed  Google Scholar 

  • Fernandez AM, de la Vega AG, Torres-Aleman L (1998) Insulinlike growth factor 1 restored motor coordination in a rat model of cerebellar ataxia. Proc Natl Acad Sci U S A 95:1253–1258

    PubMed Central  CAS  PubMed  Google Scholar 

  • Grüsser-Cornehls U, Grüsser C, Bäurle J (1999) Vermectomy enhances ovalbumin expression and improves motor performance in Weaver mutant mice, an animal model of cerebellar ataxia. Neuroscience 91:315–326

    PubMed  Google Scholar 

  • Harding HE (1984) The hereditary ataxias and related disorders. Churchill Livingstone, Edinburgh

    Google Scholar 

  • Kaiserlian D, Savino W, Uriel J, Hassid J, Dardenne M, Bach JF (1986) The wasted mutant mouse. LL Immunological abnormalities in a mouse model of ataxia-telangiectasia. Clin Exp Immunol 63:562–569

    PubMed Central  CAS  PubMed  Google Scholar 

  • Kato M, Hosokawa S, Tobimatsu S, Kuriowa Y (1982) Increased local cerebral glucose utilization in the basal ganglia of the rolling mouse Nagoya. J Cereb Blood Flow Metab 2:385–393

    CAS  PubMed  Google Scholar 

  • Niimi M, Takahara J, Aoki Y, Fujino H, Ofuji T (1982) A cerebellar ataxic rat produced by kainic acid and changes in concentrations and turnover rates of catecholamines in discrete brain regions. Acta Med Okayama 36:223–227

    CAS  PubMed  Google Scholar 

  • Sausbier M, Hu H, Arntz C, Feil S, Kamm S, Adelsberger H, Sausbier U, Sailer CA, Feil R, Hofmann F, Korth M, Shipston MJ, Knaus HG, Wolfer DP, Pedroarena CM, Storm JF, Ruth P (2004) Cerebellar ataxia and Purkinje cell dysfunction caused by Cα 2+-activated K+ channel deficiency. Proc Natl Acad Sci U S A 101:9474–9478

    PubMed Central  CAS  PubMed  Google Scholar 

  • Yamaguchi T, Kato M, Fukui M, Akazawa K (1992) Rolling mouse Nagoya as a mutant animal model of basal ganglia dysfunction: determination of absolute rates of local cerebral glucose utilization. Brain Res 598:38–44

    CAS  PubMed  Google Scholar 

Models of Niemann-Pick Syndrome

  • Bascunan-Castillo EC, Erickson RP, Howison CM, Hunter RJ, Heidenreich RH, Hicks C, Trouard TP, Gillies RJ (2004) Tamoxifen and vitamin E treatments delay symptoms in the mouse model of Niemann-Pick C. J Appl Genet 45:461–467

    PubMed  Google Scholar 

  • Camargo FC, Erickson RP, Garver WS, Hossain GS, Carbone PN, Heidenreich RA, Blanchard J (2001) Cyclodextrins in the treatment of a mouse model of Niemann-Pick C disease. Life Sci 70:131–142

    CAS  PubMed  Google Scholar 

  • Erickson RP, Garver WS, Camargo F, Hossain GS, Heidenreich RA (2000) Pharmacological and genetic modifications of somatic cholesterol do not substantially alter the course of CNS disease in Niemann-Pick C mice. J Inherit Metab Dis 23:54–62

    CAS  PubMed  Google Scholar 

  • Higashi Y, Murayama S, Pentchev PG, Suzuki K (1993) Cerebellar degeneration in the Niemann-Pick type C mouse. Acta Neuropathol 85:175–184

    CAS  PubMed  Google Scholar 

  • Liu Y, Wu YP, Wada R, Neufeld EB, Mullin KA, Howard AC, Pentchev PG, Vanier MT, Suzuki K, Proia RL (2000) Alleviation of neuronal ganglioside storage does not improve the clinical course of the Niemann-Pick C disease mouse. Hum Mol Genet 9:1087–1093

    CAS  PubMed  Google Scholar 

  • Loftus SK, Morris JA, Carstena ED, Gu JZ, Cummings C, Brown A, Ellison J, Ohno K, Rosenfeld MA, Tagle DA, Pentchev PG, Pavan WJ (1997) Murine model of Niemann-Pick C disease: mutation in a cholesterol homeostasis gene. Science 277:232–235

    CAS  PubMed  Google Scholar 

  • Pentchev PG, Boothe AD, Kruth HS, Weintroub H, Stivers J, Brady RO (1984) A genetic storage disorder in BALB/C mice with a metabolic block in esterification of exogenous cholesterol. J Biol Chem 259:5784–5791

    CAS  PubMed  Google Scholar 

  • Pentchev PG, Gal AE, Booth AD, Omodeo-Sale F, Fouks J, Neumeyer BA, Quirk JM, Dawson G, Brady RO (1980) A lysosomal storage disorder in mice characterized by a dual deficiency of sphingomyelinase and glucocerebrosidase. Biochim Biophys Acta 619:669–679

    CAS  PubMed  Google Scholar 

  • Sym M, Basson M, Johnson C (2000) A model for Niemann-Pick type C disease in the nematode Caenorhabditis elegans. Curr Biol 10:527–530

    CAS  PubMed  Google Scholar 

  • Weintraub H, Abramovici A, Sandbank U, Pentchev PG, Brady RO, Sekine M, Suzuki A, Sela B (1985) Neurological mutation characterized by demyelination in NCTR-Balb/C mouse with lysosomal lipid storage disease. J Neurochem 45:665–672

    CAS  PubMed  Google Scholar 

  • Weintraub H, Abramovici A, Sandbank U, Booth AD, Pentchev PG, Sela B (1987) Demyelination on NCTRBalb/C mouse mutant with a lysosomal storage disorder. Morphological survey. Acta Neuropathol 74:374–381

    CAS  PubMed  Google Scholar 

  • Zhang M, Chakrabarty P, Bu B, Vincent I (2004) Cyclin-dependent kinase inhibitors attenuate protein hyperphosphorylation, cytoskeletal lesion formation, and motor defects in Niemann-Pick type C mice. Am J Pathol 165:843–853

    PubMed Central  CAS  PubMed  Google Scholar 

Models of Gangliosidosis

  • Callahan JW (1999) Molecular basis of GM1 gangliosidosis and Morquio disease, type B. Structure-function studies of lysosomal β-galactosidase and the non-lysosomal β-galactosidase-like protein. Biochim Biophys Acta 1455:85–103

    CAS  PubMed  Google Scholar 

  • Cork LC, Munnell JF, Lorenz MD, Murphy JV, Baker HJ, Rattazzi MG (1977) GM2 ganglioside lysosomal storage disease in cats with β-hesosaminidase deficiency. Science 196:1014–1017

    CAS  PubMed  Google Scholar 

  • Fox J, Li YT, Dawson G, Alleman A, Johnsrude J, Schumacher J, Homer B (1999) Naturally occurring GM2 gangliosidosis in two Muntjak deer with pathological and biochemical features of human classical Tay-Sachs disease (type B GM2 gangliosidosis). Acta Neuropathol 97:57–62

    CAS  PubMed  Google Scholar 

  • Glaros EN, Kim WS, Quinn CM, Wong J, Gelissen I, Jessup W, Garner B (2005) Glycosphingolipid accumulation inhibits cholesterol efflux via the ABCA1/apolipoprotein A-I pathway. 1-Phenyl-decanoylamino-3-morpholino-1-propanol is a novel cholesterol efflux accelerator. J Biol Chem 280:24515–24523

    CAS  PubMed  Google Scholar 

  • Hahn CN, del Pilar MM, Schröder M, Vanier MT, Hara Y, Suzuki K, Suzuki K, d’Azzo A (1997) Generalized CND disease and massive GM1-ganglioside accumulation in mice defective in lysosomal acid β-galactosidase. Hum Mol Genet 6:205–211

    CAS  PubMed  Google Scholar 

  • Huang JQ, Trasler JM, Igdoura S, Michaud J, Hanai N, Gravel RA (1997) Apoptotic cell death in mouse models of GM2 gangliosidosis and observations in human Tay-Sachs and Sandhoff disease. Hum Mol Genet 6:1879–1885

    CAS  PubMed  Google Scholar 

  • Itoh M, Matsuda J, Suzuki O, Ogura A, Oshima A, Tai T, Suzuki Y, Takashima S (2001) Development of lysosomal storage in mice with targeted disruption of the β-galactosidase gene: a model of GM1-gangliosidossi. Brain Dev 23:379–384

    CAS  PubMed  Google Scholar 

  • Jeyakumar M, Butters TD, Cortina-Borja M, Hunnam V, Proia RL, Perry VH, Dwek RA, Platt FM (1999) Delayed symptom onset and increased life expectancy in Sandhoff disease mice treated with N-butyldeoxynojirimycin. Proc Natl Acad Sci U S A 96:6388–6393

    PubMed Central  CAS  PubMed  Google Scholar 

  • Jeyakumar M, Thomas R, Elliot-Smith E, Smith SA, van der Spoel AC, d’Azzo A, Perry HV, Butters TD, Dwek RA, Platt FM (2003) Central nervous system inflammation is a hallmark of pathogenesis in mouse models of GM1 and GM2 gangliosidosis. Brain 126:974–987

    CAS  PubMed  Google Scholar 

  • Kaye EM, Alroy J, Raghavan SS, Schwarting GA, Adelman LS, Runge V, Geblum D, Thalhammer JG, Zuniga G (1992) Dysmyelinogenesis in animal model of gangliosidosis. Pediatr Neurol 8:255–261

    CAS  PubMed  Google Scholar 

  • Kolter T, Sandhoff K (1998) Recent advances in the biochemistry of sphingolipidoses. Brain Pathol 8:79–100

    CAS  PubMed  Google Scholar 

  • Kosanke SD, Pierce KR, Bay WW (1978) Clinical and biochemical markers in porcine GM2-gangliosodosis. Vet Pathol 15:685–699

    CAS  PubMed  Google Scholar 

  • Kreutzer R, Leeb T, Muller G, Moritz A, Baumgartnet W (2005) A duplication of the canine β-galactosidase gene GLB1 causes exon skipping and GM1-gangliosodosis in Alaskan huskies. Genetics 170:1857–1861

    PubMed Central  CAS  PubMed  Google Scholar 

  • Kroll RA, Ma P, Roman-Goldstein S, Barkovich J, D’Agostino AN, Neuwelt EA (1995) White matter changes associated with feline GM2 gangliosidosis (Sandhoff disease): correlation of MR findings with pathologic and ultrastructural abnormalities. Am J Neuroradiol 16:1219–1226

    CAS  PubMed  Google Scholar 

  • Martin DR, Cox NR, Morrison NE, Kennamer DM, Peck SL, Dodson AN, Gentry AS, Griffin B, Rolsma MD, Baker HJ (2005) Mutation of the GM2 activator protein in a feline model of GM2 gangliosidosis. Acta Neuropathol 110:443–450

    CAS  PubMed  Google Scholar 

  • Martino S, Cavalieri C, Emiliani C, Dolcetta D, Cusella de Angelis MG, Chigorni V, Severini GM, Sandhoff K, Bordignon C, Sonnino S, Orlacchio A (2002) Restoration of the GM2 ganglioside metabolism in bone-marrow-derived stromal cells from Tay-Sachs disease animal model. Neurochem Res 27:793–800

    CAS  PubMed  Google Scholar 

  • Martino S, Marconi P, Tancini B, Dolcetta D, de Angelis MG, Montanucci P, Bregola G, Sandhoff K, Bordignon C, Emiliani C, Manservigi R, Orlacchio A (2005) A direct gene strategy via brain internal capsule reverses the biochemical defect in Tay-Sachs disease. Hum Mol Genet 14:2113–2123

    CAS  PubMed  Google Scholar 

  • Matsuda J, Suzuki O, Oshima A, Ogura A, Noguchi Y, Yamamoto Y, Asano T, Takimoto K, Sukegawa K, Suzuki Y, Naiki M (1997a) β-Galactosidase-deficient mouse as an animal model for GM1-gangliosidoses. Glycoconj J 14:729–738

    CAS  PubMed  Google Scholar 

  • Matsuda J, Suzuki O, Oshima A, Ogura A, Naiki M, Suzuki Y (1997b) Neurological manifestations of knockout mice with β-galactosidase deficiency. Brain Dev 19:19–20

    CAS  PubMed  Google Scholar 

  • Matsuda J, Suzuki O, Oshima A, Yamamoto Y, Noguchi A, Takimoto K, Itoh M, Matsuzaki Y, Yasuda Y, Ogawa S, Sakata Y, Nanba E, Higaki K, Ogawa Y, Tominaga L, Ohno K, Iwasaki H, Watanabe H, Brady RO, Suzuki Y (2003) Chemical chaperone therapy for brain pathology in GM1-gangliosidosis. Proc Natl Acad Sci U S A 100:15912–15917

    PubMed Central  CAS  PubMed  Google Scholar 

  • Muldoon LL, Neuwelt EA, Pagel MA, Weiss DL (1994) Characterization of the molecular defect in a feline model for type II GM2-gangliosidosis (Sandhoff disease). Am J Pathol 144:1109–1118

    PubMed Central  CAS  PubMed  Google Scholar 

  • Neuwelt EA, Johnson WG, Blank NK, Pagel MA, Maslen-McClure C, McClure MJ, Wu PM (1985) Characterization of a new model of GM2-gangliosidosis (Sandhoff’s disease) in Korat cats. J Clin Invest 76:482–490

    PubMed Central  CAS  PubMed  Google Scholar 

  • O’Dowd BF, Klavins MH, Willard HF, Gravel R, Lowden JA, Mahuran DJ (1986) Molecular heterogeneity in the infantile and juvenile form of Sandhoff disease (O-variant GM2 gangliosidosis). J Biol Chem 261:12680–12685

    PubMed  Google Scholar 

  • Oshima A (1998) GM1-ganglioside knockout mouse. No To Hattatsu 30:148–151

    CAS  PubMed  Google Scholar 

  • Paw BH, Kaback MM, Neufeld EF (1989) Molecular basis of adult-onset and chronic GM2 gangliosidoses in patients of Askenazi Jewish origin: substitution of serine for glycine at position 269 of the α-subunit of β-hexosaminidase. Proc Natl Acad Sci U S A 86:2413–2417

    PubMed Central  CAS  PubMed  Google Scholar 

  • Ryder SJ, Simmons MM (2001) A lysosomal storage disease of Rommey sheep that resembles human type 3GM1 gangliosidosis. Acta Neuropathol 101:225–228

    CAS  PubMed  Google Scholar 

  • Schröder M, Schnabel D, Suzuki K, Sandhoff K (1991) A mutation in the gene of a glycolipid-binding protein (GM2 activator) that causes GM2-gangluiosidosis variant AB. FEBS Lett 290:1–3

    PubMed  Google Scholar 

  • Singer HS, Cork LC (1989) Canine GM2 gangliosidosis: morphological and biochemical analysis. Vet Pathol 26:114–120

    CAS  PubMed  Google Scholar 

  • Skelly BJ, Jeffrey M, Franklin RJ, Winchester BG (1995) A new form of GM1-gangliosidosis. Acta Neuropathol 89:374–379

    CAS  PubMed  Google Scholar 

  • Wang ZH, Zeng B, Shibuya H, Johnson GS, Alroy J, Pastores GM, Raghavan S, Kolodny EH (2000) Isolation and characterization of the normal canine β-galactosidase gene and its mutation in a dog model of GM1-gangliosidosis. J Inherit Metab Dis 12:593–606

    Google Scholar 

  • Yamaguchi A, Katsuyama K, Suzuki K, Kosaka K, Aoki I, Yamanak S (2003) Plasmid-based gene transfer ameliorates visceral storage in a mouse model of Sandhoff disease. J Mol Med 81:185–193

    CAS  PubMed  Google Scholar 

  • Yamato O, Masuoka Y, Yonemura M, Hatakeyama A, Satoh H, Kobayashi A, Nakayama M, Asano T, Shoda T, Yamasaki M, Ochiai K, Umemura T, Maede Y (2003) Clinical and clinico-pathologic characteristics of Shiba dogs with a deficiency of lysosomal β-galactosidase: a canine model of human GM1 gangliosidosis. J Vet Med Sci 65:213–217

    CAS  PubMed  Google Scholar 

  • Yamato O, Matsunaga S, Takeda K, Uetsuka K, Satoh H, Shoda T, Baba Y, Yasoshima A, Kato K, Takahashi K, Yamasaki M, Nakayama H, Doi K, Maede Y, Ogawa H (2004a) GM2-gangliosidosis variant 0 (Sandhoff-like disease) in a family of Japanese domestic cats. Vet Rec 155:739–744

    CAS  PubMed  Google Scholar 

  • Yamato O, Jo EO, Shoda T, Yamsaki M, Maede Y (2004b) Rapid and simple mutation screening of GM1 gangliosidosis in Shiba dogs by direct amplification of deoxyribonucleic acid from various forms of canine whole-blood species. J Vet Diagn Invest 16:469–472

    PubMed  Google Scholar 

Models of Mucopolysaccharidosis

  • Aronovich EL, Carmichael KP, Morizono H, Koutlas IG, Deanching M, Hoganson G, Fischer A, Whitley CB (2000) Canine heparin sulfate sulfamidase and the molecular pathology underlying Sanfilippo syndrome type A in Dachshunds. Genomics 68:80–84

    CAS  PubMed  Google Scholar 

  • Aronovich EL, Johnston JM, Wang P, Giger U, Whitley CB (2001) Molecular basis for mucopolysaccharidosis type IIIB in emu (Dromaius novaehollandiae): an avian model of Sanfilippo syndrome type B. Genomics 74:299–305

    CAS  PubMed  Google Scholar 

  • Bhattacharyya R, Gliddon B, Beccarai T, Hopwood JJ, Stamley P (2001) A novel missense mutation in lysosomal sulfamidase is the basis of MPS III A in a spontaneous mouse mutant. Glycobiology 11:99–103

    CAS  PubMed  Google Scholar 

  • Bhaumik M, Muller VJ, Rozaklis T, Johnson L, Dobrenis K, Bhattacharyya R, Wurzelmann S, Finamore P, Hopwood JJ, Walkley SU, Stanley P (1999) A mouse model for mucopolysaccharidosis type III A (Sanfilippo syndrome). Glycobiology 9:1389–1396

    CAS  PubMed  Google Scholar 

  • Di Natale P, Di Domenico C, Gargiulo N, Castaldo S, Gonzalez Y, Reyero E, Mithbaokar P, de Felice M, Follenzi A, Naldini L, Villani GR (2005) Treatment of the mouse model of mucopolysaccharidosis type IIIB with lentiviral NAGLU vector. Biochem J 388:639–646

    PubMed Central  PubMed  Google Scholar 

  • Ellinwood NM, Wang P, Skeen T, Sharp NJ, Cesta M, Decker S, Edwards NJ, Bublot I, Thompson JN, Bush W, Hardam E, Haskins ME, Giger U (2003) A model of mucopolysaccharidosis IIIB (Sanfilippo syndrome IIIB): N-acetyl-a-d-glucosaminidase deficiency in Schipperke dogs. J Inherit Metab Dis 26:489–504

    CAS  PubMed  Google Scholar 

  • Fischer A, Carmichael KP, Munnell JF, Jhabvala P, Thompson JN, Matalon R, Jezyl PF, Wang P, Giger U (1998) Sulfamidase deficiency in a family of Dachshunds: a canine model of mucopolysaccharidosis IIIA (Sanfilippo A). Pediatr Res 44:74–82

    CAS  PubMed  Google Scholar 

  • Garbuzova-Davis S, Willing AE, Desjarlais T, Davis-Sanberg C, Sanberg PR (2005) Transplantation of human umbilical cord blood cells benefits an animal model of Sanfilippo syndrome type B. Stem Cells Dev 14:384–394

    CAS  PubMed  Google Scholar 

  • Giger U, Shivaprasad H, Wang P, Jezyk P, Pazzerson D, Bradley G (1997) Mucopolysaccharidosis type III B (Sanfilippo B syndrome) in emus. Vet Pathol 34:473

    Google Scholar 

  • Gliddon BL, Hopwood JJ (2004) Enzyme-replacement therapy from birth delays the development of behavior and learning problems in mucopolysaccharidosis type IIIA mice. Pediatr Res 56:65–72

    CAS  PubMed  Google Scholar 

  • Gografe SI, Garbuzova-Davis S, Willing AE, Haas K, Chamizo W, Sanberg PR (2003) Mouse model of Sanfilippo syndrome type B: relation of phenotypic features to background strain. Comp Med 53:622–632

    CAS  PubMed  Google Scholar 

  • Hemsley KM, Hopwood JJ (2005) Development of motor deficits in a murine model of mucopolysaccharidosis type IIIA (MPS-IIIA). Behav Brain Res 158:191–199

    CAS  PubMed  Google Scholar 

  • Li HH, Yu WH, Rozengurt N, Zhao HZ, Lyons KM, Anagnostaras S, Fanselow MS, Suzuki K, Vanier MT, Neufeld EF (1999) Mouse model of Sanfilippo syndrome type B produced by targeted disruption of the gene encoding α-N acetylglucosaminidase. Proc Natl Acad Sci U S A 96:14505–14510

    PubMed Central  CAS  PubMed  Google Scholar 

  • Li HH, Zhao HZ, Neufeld EF, Cai Y, Gomez-Pinilla F (2002) Attenuated plasticity in neurons and astrocytes in the mouse model of Sanfilippo syndrome type B. J Neurosci Res 69:30–38

    CAS  PubMed  Google Scholar 

  • Thompson JN, Jones MZ, Dawson G, Huffman PS (1992) N-acetylglucosamine 6-sulphatase deficiency in a Nubian goat: a model of Sanfilippo syndrome type D (mucopolysaccharidosis IIID). J Inherit Metab Dis 15:760–766

    CAS  PubMed  Google Scholar 

  • Yu WH, Zhao KW, Ryaznatsev S, Rosengurt N, Neufeld EF (2000) Short-term enzyme replacement in the mouse model of Sanfilippo syndrome B. Mol Genet Metab 71:573–580

    CAS  PubMed  Google Scholar 

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    Mary Jeanne Kallman

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    Franz J. Hock

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Kallman, M.J. (2016). Animal Models of Neurological Disorders. In: Hock, F. (eds) Drug Discovery and Evaluation: Pharmacological Assays. Springer, Cham. https://doi.org/10.1007/978-3-319-05392-9_33

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