Advertisement

Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

Transgenic zebrafish models of neurodegenerative diseases

Abstract

Since the introduction of the zebrafish as a model for the study of vertebrate developmental biology, an extensive array of techniques for its experimental manipulation and analysis has been developed. Recently it has become apparent that these powerful methodologies might be deployed in order to elucidate the pathogenesis of human neurodegenerative diseases and to identify candidate therapeutic approaches. In this article, we consider evidence that the zebrafish central nervous system provides an appropriate setting in which to model human neurological disease and we review techniques and resources available for generating transgenic models. We then examine recent publications showing that appropriate phenotypes can be provoked in the zebrafish through transgenic manipulations analogous to genetic abnormalities known to cause human tauopathies, polyglutamine diseases or motor neuron degenerations. These studies show proof of concept that findings in zebrafish models can be applicable to the pathogenic mechanisms underlying human diseases. Consequently, the prospects for providing novel insights into neurodegenerative diseases by exploiting transgenic zebrafish models and discovery-driven approaches seem favorable.

This is a preview of subscription content, log in to check access.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

References

  1. Abeliovich A, Schmitz Y, Farinas I, Choi-Lundberg D, Ho WH, Castillo PE, Shinsky N, Verdugo JM, Armanini M, Ryan A, Hynes M, Phillips H, Sulzer D, Rosenthal A (2000) Mice lacking alpha-synuclein display functional deficits in the nigrostriatal dopamine system. Neuron 25:239–252

  2. Airhart MJ, Lee DH, Wilson TD, Miller BE, Miller MN, Skalko RG (2007) Movement disorders and neurochemical changes in zebrafish larvae after bath exposure to fluoxetine (PROZAC). Neurotoxicol Teratol 29:652–664

  3. Amsterdam A, Burgess S, Golling G, Chen W, Sun Z, Townsend K, Farrington S, Haldi M, Hopkins N (1999) A large-scale insertional mutagenesis screen in zebrafish. Genes Dev 13:2713–2724

  4. Anichtchik OV, Kaslin J, Peitsaro N, Scheinin M, Panula P (2004) Neurochemical and behavioural changes in zebrafish Danio rerio after systemic administration of 6-hydroxydopamine and 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine. J Neurochem 88:443–453

  5. Anichtchik O, Diekmann H, Fleming A, Roach A, Goldsmith P, Rubinsztein DC (2008) Loss of PINK1 function affects development and results in neurodegeneration in zebrafish. J Neurosci 28:8199–8207

  6. Asakawa K, Suster ML, Mizusawa K, Nagayoshi S, Kotani T, Urasaki A, Kishimoto Y, Hibi M, Kawakami K (2008) Genetic dissection of neural circuits by Tol2 transposon-mediated Gal4 gene and enhancer trapping in zebrafish. Proc Natl Acad Sci USA 105:1255–1260

  7. Bae YK, Kani S, Shimizu T, Tanabe K, Nojima H, Kimura Y, Higashijima S, Hibi M (2009) Anatomy of zebrafish cerebellum and screen for mutations affecting its development. Dev Biol 330:406–426

  8. Bai Q, Burton EA (2009) Cis-acting elements responsible for dopaminergic neuron-specific expression of zebrafish slc6a3 (dopamine transporter) in vivo are located remote from the transcriptional start site. Neuroscience 164:1138–1151

  9. Bai Q, Mullett SJ, Garver JA, Hinkle DA, Burton EA (2006) Zebrafish DJ-1 is evolutionarily conserved and expressed in dopaminergic neurons. Brain Res 1113:33–44

  10. Bai Q, Garver JA, Hukriede NA, Burton EA (2007) Generation of a transgenic zebrafish model of Tauopathy using a novel promoter element derived from the zebrafish eno2 gene. Nucleic Acids Res 35:6501–6516

  11. Bai Q, Wei X, Burton EA (2009) Expression of a 12-kb promoter element derived from the zebrafish enolase-2 gene in the zebrafish visual system. Neurosci Lett 449:252–257

  12. Baulac S, Lu H, Strahle J, Yang T, Goldberg MS, Shen J, Schlossmacher MG, Lemere CA, Lu Q, Xia W (2009) Increased DJ-1 expression under oxidative stress and in Alzheimer’s disease brains. Mol Neurodegener 4:12

  13. Becker CG, Becker T (2008) Adult zebrafish as a model for successful central nervous system regeneration. Restor Neurol Neurosci 26:71–80

  14. Bernardos RL, Raymond PA (2006) GFAP transgenic zebrafish. Gene Expr Patterns 6:1007–1013

  15. Boehmler W, Obrecht-Pflumio S, Canfield V, Thisse C, Thisse B, Levenson R (2004) Evolution and expression of D2 and D3 dopamine receptor genes in zebrafish. Dev Dyn 230:481–493

  16. Boehmler W, Carr T, Thisse C, Thisse B, Canfield VA, Levenson R (2007) D4 Dopamine receptor genes of zebrafish and effects of the antipsychotic clozapine on larval swimming behaviour. Genes Brain Behav 6:155–166

  17. Bonifati V, Rizzu P, Squitieri F, Krieger E, Vanacore N, van Swieten JC, Brice A, van Duijn CM, Oostra B, Meco G, Heutink P (2003) DJ-1(PARK7), a novel gene for autosomal recessive, early onset Parkinsonism. Neurol Sci 24:159–160

  18. Bretaud S, Lee S, Guo S (2004) Sensitivity of zebrafish to environmental toxins implicated in Parkinson’s disease. Neurotoxicol Teratol 26:857–864

  19. Bretaud S, Allen C, Ingham PW, Bandmann O (2007) p53-dependent neuronal cell death in a DJ-1-deficient zebrafish model of Parkinson’s disease. J Neurochem 100:1626–1635

  20. Brockerhoff SE, Hurley JB, Janssen-Bienhold U, Neuhauss SC, Driever W, Dowling JE (1995) A behavioral screen for isolating zebrafish mutants with visual system defects. Proc Natl Acad Sci USA 92:10545–10549

  21. Brustein E, Chong M, Holmqvist B, Drapeau P (2003) Serotonin patterns locomotor network activity in the developing zebrafish by modulating quiescent periods. J Neurobiol 57:303–322

  22. Cadieux B, Chitramuthu BP, Baranowski D, Bennett HP (2005) The zebrafish progranulin gene family and antisense transcripts. BMC Genom 6:156

  23. Campbell WA, Yang H, Zetterberg H, Baulac S, Sears JA, Liu T, Wong ST, Zhong TP, Xia W (2006) Zebrafish lacking Alzheimer presenilin enhancer 2 (Pen-2) demonstrate excessive p53-dependent apoptosis and neuronal loss. J Neurochem 96:1423–1440

  24. Candy J, Collet C (2005) Two tyrosine hydroxylase genes in teleosts. Biochim Biophys Acta 1727:35–44

  25. Carlson KM, Melcher L, Lai S, Zoghbi HY, Clark HB, Orr HT (2009) Characterization of the zebrafish atxn1/axh gene family. J Neurogenet 23:313–323

  26. Chen YH, Wang YH, Chang MY, Lin CY, Weng CW, Westerfield M, Tsai HJ (2007) Multiple upstream modules regulate zebrafish myf5 expression. BMC Dev Biol 7:1

  27. Chen M, Martins RN, Lardelli M (2009a) Complex splicing and neural expression of duplicated tau genes in zebrafish embryos. J Alzheimers Dis 18(2):305–317

  28. Chen YC, Cheng CH, Chen GD, Hung CC, Yang CH, Hwang SP, Kawakami K, Wu BK, Huang CJ (2009b) Recapitulation of zebrafish sncga expression pattern and labeling the habenular complex in transgenic zebrafish using green fluorescent protein reporter gene. Dev Dyn 238:746–754

  29. Chen YC, Priyadarshini M, Panula P (2009c) Complementary developmental expression of the two tyrosine hydroxylase transcripts in zebrafish. Histochem Cell Biol 132(4):375–381

  30. Clark IE, Dodson MW, Jiang C, Cao JH, Huh JR, Seol JH, Yoo SJ, Hay BA, Guo M (2006) Drosophila pink1 is required for mitochondrial function and interacts genetically with parkin. Nature 441:1162–1166

  31. Clayton DF, George JM (1998) The synucleins: a family of proteins involved in synaptic function, plasticity, neurodegeneration and disease. Trends Neurosci 21:249–254

  32. Deng HX, Hentati A, Tainer JA, Iqbal Z, Cayabyab A, Hung WY, Getzoff ED, Hu P, Herzfeldt B, Roos RP et al (1993) Amyotrophic lateral sclerosis and structural defects in Cu, Zn superoxide dismutase. Science 261:1047–1051

  33. Diekmann H, Anichtchik O, Fleming A, Futter M, Goldsmith P, Roach A, Rubinsztein DC (2009) Decreased BDNF levels are a major contributor to the embryonic phenotype of huntingtin knockdown zebrafish. J Neurosci 29:1343–1349

  34. Distel M, Wullimann MF, Koster RW (2009) Optimized Gal4 genetics for permanent gene expression mapping in zebrafish. Proc Natl Acad Sci USA 106:13365–13370

  35. Doyon Y, McCammon JM, Miller JC, Faraji F, Ngo C, Katibah GE, Amora R, Hocking TD, Zhang L, Rebar EJ, Gregory PD, Urnov FD, Amacher SL (2008) Heritable targeted gene disruption in zebrafish using designed zinc-finger nucleases. Nat Biotechnol 26:702–708

  36. Driever W, Solnica-Krezel L, Schier AF, Neuhauss SC, Malicki J, Stemple DL, Stainier DY, Zwartkruis F, Abdelilah S, Rangini Z, Belak J, Boggs C (1996) A genetic screen for mutations affecting embryogenesis in zebrafish. Development 123:37–46

  37. Fan J, Ren H, Jia N, Fei E, Zhou T, Jiang P, Wu M, Wang G (2008) DJ-1 decreases Bax expression through repressing p53 transcriptional activity. J Biol Chem 283:4022–4030

  38. Flinn L, Mortiboys H, Volkmann K, Koster RW, Ingham PW, Bandmann O (2009) Complex I deficiency and dopaminergic neuronal cell loss in parkin-deficient zebrafish (Danio rerio). Brain 132:1613–1623

  39. Gao Y, Li P, Li L (2005) Transgenic zebrafish that express tyrosine hydroxylase promoter in inner retinal cells. Dev Dyn 233:921–929

  40. Giacomini NJ, Rose B, Kobayashi K, Guo S (2006) Antipsychotics produce locomotor impairment in larval zebrafish. Neurotoxicol Teratol 28:245–250

  41. Goedert M, Spillantini MG, Jakes R, Rutherford D, Crowther RA (1989) Multiple isoforms of human microtubule-associated protein tau: sequences and localization in neurofibrillary tangles of Alzheimer’s disease. Neuron 3:519–526

  42. Grabher C, Wittbrodt J (2008) Recent advances in meganuclease-and transposon-mediated transgenesis of medaka and zebrafish. Methods Mol Biol 461:521–539

  43. Groth C, Nornes S, McCarty R, Tamme R, Lardelli M (2002) Identification of a second presenilin gene in zebrafish with similarity to the human Alzheimer’s disease gene presenilin2. Dev Genes Evol 212:486–490

  44. Guo S, Wilson SW, Cooke S, Chitnis AB, Driever W, Rosenthal A (1999) Mutations in the zebrafish unmask shared regulatory pathways controlling the development of catecholaminergic neurons. Dev Biol 208:473–487

  45. Higashijima S, Okamoto H, Ueno N, Hotta Y, Eguchi G (1997) High-frequency generation of transgenic zebrafish which reliably express GFP in whole muscles or the whole body by using promoters of zebrafish origin. Dev Biol 192:289–299

  46. Hutton M, Lendon CL, Rizzu P, Baker M, Froelich S, Houlden H, Pickering-Brown S, Chakraverty S, Isaacs A, Grover A, Hackett J, Adamson J, Lincoln S, Dickson D, Davies P, Petersen RC, Stevens M, de Graaff E, Wauters E, van Baren J, Hillebrand M, Joosse M, Kwon JM, Nowotny P, Heutink P et al (1998) Association of missense and 5′-splice-site mutations in tau with the inherited dementia FTDP-17. Nature 393:702–705

  47. Imamura S, Kishi S (2005) Molecular cloning and functional characterization of zebrafish ATM. Int J Biochem Cell Biol 37:1105–1116

  48. Imbert G, Saudou F, Yvert G, Devys D, Trottier Y, Garnier JM, Weber C, Mandel JL, Cancel G, Abbas N, Durr A, Didierjean O, Stevanin G, Agid Y, Brice A (1996) Cloning of the gene for spinocerebellar ataxia 2 reveals a locus with high sensitivity to expanded CAG/glutamine repeats. Nat Genet 14:285–291

  49. Jacquier A, Dujon B (1985) An intron-encoded protein is active in a gene conversion process that spreads an intron into a mitochondrial gene. Cell 41:383–394

  50. Jeong JY, Kwon HB, Ahn JC, Kang D, Kwon SH, Park JA, Kim KW (2008) Functional and developmental analysis of the blood–brain barrier in zebrafish. Brain Res Bull 75:619–628

  51. Kapsimali M, Vidal B, Gonzalez A, Dufour S, Vernier P (2000) Distribution of the mRNA encoding the four dopamine D(1) receptor subtypes in the brain of the european eel (Anguilla anguilla): comparative approach to the function of D(1) receptors in vertebrates. J Comp Neurol 419:320–343

  52. Karlovich CA, John RM, Ramirez L, Stainier DY, Myers RM (1998) Characterization of the Huntington’s disease (HD) gene homologue in the zebrafish Danio rerio. Gene 217:117–125

  53. Kawaguchi Y, Okamoto T, Taniwaki M, Aizawa M, Inoue M, Katayama S, Kawakami H, Nakamura S, Nishimura M, Akiguchi I et al (1994) CAG expansions in a novel gene for Machado-Joseph disease at chromosome 14q32.1. Nat Genet 8:221–228

  54. Kawai H, Arata N, Nakayasu H (2001) Three-dimensional distribution of astrocytes in zebrafish spinal cord. Glia 36:406–413

  55. Kawakami K (2004) Transgenesis and gene trap methods in zebrafish by using the Tol2 transposable element. Methods Cell Biol 77:201–222

  56. Kawakami K, Shima A, Kawakami N (2000) Identification of a functional transposase of the Tol2 element, an Ac-like element from the Japanese medaka fish, and its transposition in the zebrafish germ lineage. Proc Natl Acad Sci USA 97:11403–11408

  57. Kawakami K, Takeda H, Kawakami N, Kobayashi M, Matsuda N, Mishina M (2004) A transposon-mediated gene trap approach identifies developmentally regulated genes in zebrafish. Dev Cell 7:133–144

  58. Kim CH, Ueshima E, Muraoka O, Tanaka H, Yeo SY, Huh TL, Miki N (1996) Zebrafish elav/HuC homologue as a very early neuronal marker. Neurosci Lett 216:109–112

  59. Kimmel CB (1993) Patterning the brain of the zebrafish embryo. Annu Rev Neurosci 16:707–732

  60. Kirby BB, Takada N, Latimer AJ, Shin J, Carney TJ, Kelsh RN, Appel B (2006) In vivo time-lapse imaging shows dynamic oligodendrocyte progenitor behavior during zebrafish development. Nat Neurosci 9:1506–1511

  61. Koga A, Suzuki M, Inagaki H, Bessho Y, Hori H (1996) Transposable element in fish. Nature 383:30

  62. Lam CS, Korzh V, Strahle U (2005) Zebrafish embryos are susceptible to the dopaminergic neurotoxin MPTP. Eur J Neurosci 21:1758–1762

  63. Landles C, Bates GP (2004) Huntingtin and the molecular pathogenesis of Huntington’s disease. Fourth in molecular medicine review series. EMBO Rep 5:958–963

  64. Lee EC, Yu D, Martinez de Velasco J, Tessarollo L, Swing DA, Court DL, Jenkins NA, Copeland NG (2001a) A highly efficient Escherichia coli-based chromosome engineering system adapted for recombinogenic targeting and subcloning of BAC DNA. Genomics 73:56–65

  65. Lee VM, Goedert M, Trojanowski JQ (2001b) Neurodegenerative tauopathies. Annu Rev Neurosci 24:1121–1159

  66. Leimer U, Lun K, Romig H, Walter J, Grunberg J, Brand M, Haass C (1999) Zebrafish (Danio rerio) presenilin promotes aberrant amyloid beta-peptide production and requires a critical aspartate residue for its function in amyloidogenesis. Biochemistry 38:13602–13609

  67. Lemmens R, Van Hoecke A, Hersmus N, Geelen V, D’Hollander I, Thijs V, Van Den Bosch L, Carmeliet P, Robberecht W (2007) Overexpression of mutant superoxide dismutase 1 causes a motor axonopathy in the zebrafish. Hum Mol Genet 16:2359–2365

  68. Long Q, Meng A, Wang H, Jessen JR, Farrell MJ, Lin S (1997) GATA-1 expression pattern can be recapitulated in living transgenic zebrafish using GFP reporter gene. Development 124:4105–4111

  69. Lumsden AL, Henshall TL, Dayan S, Lardelli MT, Richards RI (2007) Huntingtin-deficient zebrafish exhibit defects in iron utilization and development. Hum Mol Genet 16:1905–1920

  70. Ma PM (2003) Catecholaminergic systems in the zebrafish. IV. Organization and projection pattern of dopaminergic neurons in the diencephalon. J Comp Neurol 460:13–37

  71. Malicki J, Neuhauss SC, Schier AF, Solnica-Krezel L, Stemple DL, Stainier DY, Abdelilah S, Zwartkruis F, Rangini Z, Driever W (1996) Mutations affecting development of the zebrafish retina. Development 123:263–273

  72. Mates L, Chuah MK, Belay E, Jerchow B, Manoj N, Acosta-Sanchez A, Grzela DP, Schmitt A, Becker K, Matrai J, Ma L, Samara-Kuko E, Gysemans C, Pryputniewicz D, Miskey C, Fletcher B, Vandendriessche T, Ivics Z, Izsvak Z (2009) Molecular evolution of a novel hyperactive Sleeping Beauty transposase enables robust stable gene transfer in vertebrates. Nat Genet 41:753–761

  73. McGraw HF, Nechiporuk A, Raible DW (2008) Zebrafish dorsal root ganglia neural precursor cells adopt a glial fate in the absence of neurogenin1. J Neurosci 28:12558–12569

  74. McKinley ET, Baranowski TC, Blavo DO, Cato C, Doan TN, Rubinstein AL (2005) Neuroprotection of MPTP-induced toxicity in zebrafish dopaminergic neurons. Brain Res Mol Brain Res 141:128–137

  75. McNaught KS, Belizaire R, Isacson O, Jenner P, Olanow CW (2003) Altered proteasomal function in sporadic Parkinson’s disease. Exp Neurol 179:38–46

  76. Meng A, Tang H, Ong BA, Farrell MJ, Lin S (1997) Promoter analysis in living zebrafish embryos identifies a cis-acting motif required for neuronal expression of GATA-2. Proc Natl Acad Sci USA 94:6267–6272

  77. Meng S, Ryu S, Zhao B, Zhang DQ, Driever W, McMahon DG (2008a) Targeting retinal dopaminergic neurons in tyrosine hydroxylase-driven green fluorescent protein transgenic zebrafish. Mol Vis 14:2475–2483

  78. Meng X, Noyes MB, Zhu LJ, Lawson ND, Wolfe SA (2008b) Targeted gene inactivation in zebrafish using engineered zinc-finger nucleases. Nat Biotechnol 26:695–701

  79. Miller VM, Nelson RF, Gouvion CM, Williams A, Rodriguez-Lebron E, Harper SQ, Davidson BL, Rebagliati MR, Paulson HL (2005) CHIP suppresses polyglutamine aggregation and toxicity in vitro and in vivo. J Neurosci 25:9152–9161

  80. Molina G, Vogt A, Bakan A, Dai W, Queiroz de Oliveira P, Znosko W, Smithgall TE, Bahar I, Lazo JS, Day BW, Tsang M (2009) Zebrafish chemical screening reveals an inhibitor of Dusp6 that expands cardiac cell lineages. Nat Chem Biol 5:680–687

  81. Mortiboys H, Thomas KJ et al (2008) Mitochondrial function and morphology are impaired in parkin-mutant fibroblasts. Ann Neurol 64(5):555–565

  82. Mueller T, Vernier P, Wullimann MF (2004) The adult central nervous cholinergic system of a neurogenetic model animal, the zebrafish Danio rerio. Brain Res 1011:156–169

  83. Mullett SJ, Hinkle DA (2009) DJ-1 knock-down in astrocytes impairs astrocyte-mediated neuroprotection against rotenone. Neurobiol Dis 33:28–36

  84. Musa A, Lehrach H, Russo VA (2001) Distinct expression patterns of two zebrafish homologues of the human APP gene during embryonic development. Dev Genes Evol 211:563–567

  85. Narendra D, Tanaka A, Suen DF, Youle RJ (2008) Parkin is recruited selectively to impaired mitochondria and promotes their autophagy. J Cell Biol 183:795–803

  86. Nasevicius A, Ekker SC (2000) Effective targeted gene ‘knockdown’ in zebrafish. Nat Genet 26:216–220

  87. Orr HT, Chung MY, Banfi S, Kwiatkowski TJ Jr, Servadio A, Beaudet AL, McCall AE, Duvick LA, Ranum LP, Zoghbi HY (1993) Expansion of an unstable trinucleotide CAG repeat in spinocerebellar ataxia type 1. Nat Genet 4:221–226

  88. Paquet D, Bhat R, Sydow A, Mandelkow EM, Berg S, Hellberg S, Falting J, Distel M, Koster RW, Schmid B, Haass C (2009) A zebrafish model of tauopathy allows in vivo imaging of neuronal cell death and drug evaluation. J Clin Invest 119:1382–1395

  89. Park HC, Kim CH, Bae YK, Yeo SY, Kim SH, Hong SK, Shin J, Yoo KW, Hibi M, Hirano T, Miki N, Chitnis AB, Huh TL (2000) Analysis of upstream elements in the HuC promoter leads to the establishment of transgenic zebrafish with fluorescent neurons. Dev Biol 227:279–293

  90. Peri F, Nusslein-Volhard C (2008) Live imaging of neuronal degradation by microglia reveals a role for v0-ATPase a1 in phagosomal fusion in vivo. Cell 133:916–927

  91. Reiner A, Northcutt RG (1992) An immunohistochemical study of the telencephalon of the senegal bichir (Polypterus senegalus). J Comp Neurol 319:359–386

  92. RG HDC (1993) A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington’s disease chromosomes. Cell 72:971–983

  93. Rink E, Wullimann MF (2001) The teleostean (zebrafish) dopaminergic system ascending to the subpallium (striatum) is located in the basal diencephalon (posterior tuberculum). Brain Res 889:316–330

  94. Rink E, Wullimann MF (2002) Development of the catecholaminergic system in the early zebrafish brain: an immunohistochemical study. Brain Res Dev Brain Res 137:89–100

  95. Rink E, Wullimann MF (2004) Connections of the ventral telencephalon (subpallium) in the zebrafish (Danio rerio). Brain Res 1011:206–220

  96. Riparbelli MG, Callaini G (2007) The Drosophila parkin homologue is required for normal mitochondrial dynamics during spermiogenesis. Dev Biol 303:108–120

  97. Rosen DR, Siddique T, Patterson D, Figlewicz DA, Sapp P, Hentati A, Donaldson D, Goto J, O’Regan JP, Deng HX et al (1993) Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis. Nature 362:59–62

  98. Ryu S, Holzschuh J, Mahler J, Driever W (2006) Genetic analysis of dopaminergic system development in zebrafish. J Neural Transm Suppl (70):61–66

  99. Sallinen V, Torkko V, Sundvik M, Reenila I, Khrustalyov D, Kaslin J, Panula P (2009a) MPTP and MPP+ target specific aminergic cell populations in larval zebrafish. J Neurochem 108(3):719–731

  100. Sallinen V, Sundvik M, Reenila I, Peitsaro N, Khrustalyov D, Anichtchik O, Toleikyte G, Kaslin J, Panula P (2009b) Hyperserotonergic phenotype after monoamine oxidase inhibition in larval zebrafish. J Neurochem 109:403–415

  101. Sato Y, Miyasaka N, Yoshihara Y (2007) Hierarchical regulation of odorant receptor gene choice and subsequent axonal projection of olfactory sensory neurons in zebrafish. J Neurosci 27:1606–1615

  102. Scheer N, Campos-Ortega JA (1999) Use of the Gal4–UAS technique for targeted gene expression in the zebrafish. Mech Dev 80:153–158

  103. Schiffer NW, Broadley SA, Hirschberger T, Tavan P, Kretzschmar HA, Giese A, Haass C, Hartl FU, Schmid B (2007) Identification of anti-prion compounds as efficient inhibitors of polyglutamine protein aggregation in a zebrafish model. J Biol Chem 282:9195–9203

  104. Sharma SC, Berthoud VM, Breckwoldt R (1989) Distribution of substance P-like immunoreactivity in the goldfish brain. J Comp Neurol 279:104–116

  105. Shimura H, Hattori N, Kubo S, Mizuno Y, Asakawa S, Minoshima S, Shimizu N, Iwai K, Chiba T, Tanaka K, Suzuki T (2000) Familial Parkinson disease gene product, parkin, is a ubiquitin-protein ligase. Nat Genet 25:302–305

  106. Solnica-Krezel L, Schier AF, Driever W (1994) Efficient recovery of ENU-induced mutations from the zebrafish germline. Genetics 136:1401–1420

  107. Soroldoni D, Hogan BM, Oates AC (2009) Simple and efficient transgenesis with meganuclease constructs in zebrafish. Methods Mol Biol 546:117–130

  108. Spillantini MG, Crowther RA, Jakes R, Hasegawa M, Goedert M (1998) alpha-Synuclein in filamentous inclusions of Lewy bodies from Parkinson’s disease and dementia with Lewy bodies. Proc Natl Acad Sci USA 95:6469–6473

  109. Stuart GW, McMurray JV, Westerfield M (1988) Replication, integration and stable germ-line transmission of foreign sequences injected into early zebrafish embryos. Development 103:403–412

  110. Sun Z, Gitler AD (2008) Discovery and characterization of three novel synuclein genes in zebrafish. Dev Dyn 237:2490–2495

  111. Thermes V, Grabher C, Ristoratore F, Bourrat F, Choulika A, Wittbrodt J, Joly JS (2002) I-SceI meganuclease mediates highly efficient transgenesis in fish. Mech Dev 118:91–98

  112. Thirumalai V, Cline HT (2008) Endogenous dopamine suppresses initiation of swimming in prefeeding zebrafish larvae. J Neurophysiol 100:1635–1648

  113. Tomasiewicz HG, Flaherty DB, Soria JP, Wood JG (2002) Transgenic zebrafish model of neurodegeneration. J Neurosci Res 70:734–745

  114. Tu PH, Galvin JE, Baba M, Giasson B, Tomita T, Leight S, Nakajo S, Iwatsubo T, Trojanowski JQ, Lee VM (1998) Glial cytoplasmic inclusions in white matter oligodendrocytes of multiple system atrophy brains contain insoluble alpha-synuclein. Ann Neurol 44:415–422

  115. Turner BJ, Talbot K (2008) Transgenics, toxicity and therapeutics in rodent models of mutant SOD1-mediated familial ALS. Prog Neurobiol 85:94–134

  116. Valente EM, Abou-Sleiman PM, Caputo V, Muqit MM, Harvey K, Gispert S, Ali Z, Del Turco D, Bentivoglio AR, Healy DG, Albanese A, Nussbaum R, Gonzalez-Maldonado R, Deller T, Salvi S, Cortelli P, Gilks WP, Latchman DS, Harvey RJ, Dallapiccola B, Auburger G, Wood NW (2004) Hereditary early-onset Parkinson’s disease caused by mutations in PINK1. Science 304:1158–1160

  117. Vila M, Jackson-Lewis V, Guegan C, Wu DC, Teismann P, Choi DK, Tieu K, Przedborski S (2001) The role of glial cells in Parkinson’s disease. Curr Opin Neurol 14:483–489

  118. Wen L, Wei W, Gu W, Huang P, Ren X, Zhang Z, Zhu Z, Lin S, Zhang B (2008) Visualization of monoaminergic neurons and neurotoxicity of MPTP in live transgenic zebrafish. Dev Biol 314:84–92

  119. Williams A, Sarkar S, Cuddon P, Ttofi EK, Saiki S, Siddiqi FH, Jahreiss L, Fleming A, Pask D, Goldsmith P, O’Kane CJ, Floto RA, Rubinsztein DC (2008) Novel targets for Huntington’s disease in an mTOR-independent autophagy pathway. Nat Chem Biol 4:295–305

  120. Wullimann MF, Rink E (2002) The teleostean forebrain: a comparative and developmental view based on early proliferation, Pax6 activity and catecholaminergic organization. Brain Res Bull 57:363–370

  121. Wullimann MF, Rupp B, Reichert H (1996) Neuroanatomy of the zebrafish brain. Birkhauser-Verlag, Berlin

  122. Yang Z, Jiang H, Zhao F, Shankar DB, Sakamoto KM, Zhang MQ, Lin S (2007) A highly conserved regulatory element controls hematopoietic expression of GATA-2 in zebrafish. BMC Dev Biol 7:97

  123. Yang Y, Ouyang Y, Yang L, Beal MF, McQuibban A, Vogel H, Lu B (2008) Pink1 regulates mitochondrial dynamics through interaction with the fission/fusion machinery. Proc Natl Acad Sci USA 105:7070–7075

  124. Yang Z, Jiang H, Lin S (2009) Bacterial artificial chromosome transgenesis for zebrafish. Methods Mol Biol 546:103–116

  125. Yoshida M, Macklin WB (2005) Oligodendrocyte development and myelination in GFP-transgenic zebrafish. J Neurosci Res 81:1–8

  126. Yoshida H, Craxton M, Jakes R, Zibaee S, Tavare R, Fraser G, Serpell LC, Davletov B, Crowther RA, Goedert M (2006) Synuclein proteins of the pufferfish Fugu rubripes: sequences and functional characterization. Biochemistry 45:2599–2607

  127. Zoghbi HY, Orr HT (2009) Pathogenic mechanisms of a polyglutamine-mediated neurodegenerative disease, spinocerebellar ataxia type 1. J Biol Chem 284:7425–7429

  128. Zon LI, Peterson RT (2005) In vivo drug discovery in the zebrafish. Nat Rev Drug Discov 4:35–44

Download references

Author information

Correspondence to Edward A. Burton.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Sager, J.J., Bai, Q. & Burton, E.A. Transgenic zebrafish models of neurodegenerative diseases. Brain Struct Funct 214, 285–302 (2010). https://doi.org/10.1007/s00429-009-0237-1

Download citation

Keywords

  • Zebrafish
  • Neurodegeneration
  • Transgenic
  • Parkinson
  • Alzheimer
  • eno2
  • slc6a3
  • tol2
  • Parkin
  • dj1
  • Huntington