Skip to main content
SpringerLink
Log in

Mouse Models of Huntington’s Disease

  • Protocol
  • First Online:
Huntington’s Disease

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1780))

Abstract

The identification of the mutation causing Huntington’s disease (HD) has led to the generation of a large number of mouse models. These models are used to further enhance our understanding of the mechanisms underlying the disease, as well as investigating and identifying therapeutic targets for this disorder. Here we review the transgenic, knock-in mice commonly used to model HD, as well those that have been generated to study specific disease mechanisms. We then provide a brief overview of the importance of standardizing the use of HD mice and describe brief protocols used for genotyping the mouse models used within the Bates Laboratory.

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

Access this chapter

Log in via an institution
Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 189.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 249.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 329.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Bates G, Tabrizi S, Jones L (2014) Huntington’s disease, vol 64. Oxford University Press, Oxford, UK

    Google Scholar 

  2. Vonsattel J-P, Myers RH, Stevens TJ et al (1985) Neuropathological classification of Huntington’s disease. J Neuropathol Exp Neurol 44:559–577

    Article  PubMed  CAS  Google Scholar 

  3. Macdonald ME, Ambrose CM, Duyao MP et al (1993) A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntingtons-disease chromosomes. Cell 72:971–983

    Article  Google Scholar 

  4. Bayram-Weston Z, Jones L, Dunnett SB, Brooks SP (2012) Light and electron microscopic characterization of the evolution of cellular pathology in the R6/1 Huntington’s disease transgenic mice. Brain Res Bull 88:104–112

    Article  PubMed  CAS  Google Scholar 

  5. Brooks SP, Janghra N, Workman VL et al (2012) Longitudinal analysis of the behavioural phenotype in R6/1 (C57BL/6J) Huntington’s disease transgenic mice. Brain Res Bull 88:94–103

    Article  PubMed  CAS  Google Scholar 

  6. Carter RJ, Lione LA, Humby T et al (1999) Characterization of progressive motor deficits in mice transgenic for the human Huntington’s disease mutation. J Neurosci 19:3248–3257

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Cummings DM, Alaghband Y, Hickey MA et al (2012) A critical window of CAG repeat-length correlates with phenotype severity in the R6/2 mouse model of Huntington’s disease. J Neurophysiol 107:677–691

    Article  PubMed  CAS  Google Scholar 

  8. Davies SW, Turmaine M, Cozens BA et al (1997) Formation of neuronal intranuclear inclusions underlies the neurological dysfunction in mice transgenic for the HD mutation. Cell 90:537–548

    Article  PubMed  CAS  Google Scholar 

  9. Dragatsis I, Goldowitz D, Del Mar N et al (2009) CAG repeat lengths > or = 335 attenuate the phenotype in the R6/2 Huntington’s disease transgenic mouse. Neurobiol Dis 33:315–330

    Article  PubMed  CAS  Google Scholar 

  10. Mangiarini L, Sathasivam K, Seller M et al (1996) Exon 1 of the HD gene with an expanded CAG repeat is sufficient to cause a progressive neurological phenotype in transgenic mice. Cell 87:493–506

    Article  PubMed  CAS  Google Scholar 

  11. Menalled L, El-Khodor BF, Patry M et al (2009) Systematic behavioral evaluation of Huntington’s disease transgenic and knock-in mouse models. Neurobiol Dis 35:319–336

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  12. Morton AJ, Glynn D, Leavens W et al (2009) Paradoxical delay in the onset of disease caused by super-long CAG repeat expansions in R6/2 mice. Neurobiol Dis 33:331–341

    Article  PubMed  CAS  Google Scholar 

  13. Schilling G, Becher MW, Sharp AH et al (1999) Intranuclear inclusions and neuritic aggregates in transgenic mice expressing a mutant N-terminal fragment of huntingtin. Hum Mol Genet 8:397–407

    Article  PubMed  CAS  Google Scholar 

  14. Laforet GA, Sapp E, Chase K et al (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

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  15. Gray M, Shirasaki DI, Cepeda C et al (2008) Full-length human mutant huntingtin with a stable polyglutamine repeat can elicit progressive and selective neuropathogenesis in BACHD mice. J Neurosci 28:6182–6195

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  16. Van Raamsdonk JM, Metzler M, Slow E et al (2007) Phenotypic abnormalities in the YAC128 mouse model of Huntington disease are penetrant on multiple genetic backgrounds and modulated by strain. Neurobiol Dis 26:189–200

    Article  PubMed  CAS  Google Scholar 

  17. Southwell AL, Warby SC, Carroll JB et al (2013) A fully humanized transgenic mouse model of Huntington disease. Hum Mol Genet 22:18–34

    Article  PubMed  CAS  Google Scholar 

  18. Southwell AL, Skotte NH, Villanueva EB et al (2017) A novel humanized mouse model of Huntington disease for preclinical development of therapeutics targeting mutant huntingtin alleles. Hum Mol Genet 26:1115–1132

    PubMed  CAS  Google Scholar 

  19. Sathasivam K, Neueder A, Gipson TA et al (2013) Aberrant splicing of HTT generates the pathogenic exon 1 protein in Huntington disease. Proc Natl Acad Sci U S A 110:2366–2370

    Article  PubMed  PubMed Central  Google Scholar 

  20. Neueder A, Landles C, Ghosh R et al (2017) The pathogenic exon 1 HTT protein is produced by incomplete splicing in Huntington’s disease patients. Sci Rep 7:1370

    Article  CAS  Google Scholar 

  21. Mangiarini L, Sathasivam K, Mahal A et al (1997) Instability of highly expanded CAG repeats in mice transgenic for the Huntington’s disease mutation. Nat Genet 15:197–200

    Article  PubMed  CAS  Google Scholar 

  22. Mielcarek M, Landles C, Weiss A et al (2013) HDAC4 reduction: a novel therapeutic strategy to target cytoplasmic huntingtin and ameliorate neurodegeneration. PLoS Biol 11:e1001717

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  23. Li H, Li S-H, Cheng AL et al (1999) Ultrastructural localization and progressive formation of neuropil aggregates in Huntington’s disease transgenic mice. Hum Mol Genet 8:1227–1236

    Article  PubMed  CAS  Google Scholar 

  24. Sathasivam K, Lane A, Legleiter J et al (2010) Identical oligomeric and fibrillar structures captured from the brains of R6/2 and knock-in mouse models of Huntington’s disease. Hum Mol Genet 19:65–78

    Article  PubMed  CAS  Google Scholar 

  25. Stack EC, Kubilus JK, Smith K et al (2005) Chronology of behavioral symptoms and neuropathological sequela in R6/2 Huntington’s disease transgenic mice. J Comp Neurol 490:354–370

    Article  PubMed  Google Scholar 

  26. Lione LA, Carter RJ, Hunt MJ et al (1999) Selective discrimination learning impairments in mice expressing the human Huntington’s disease mutation. J Neurosci 19:10428–10437

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  27. Murphy KP, Carter RJ, Lione LA et al (2000) Abnormal synaptic plasticity and impaired spatial cognition in mice transgenic for exon 1 of the human Huntington’s disease mutation. J Neurosci 20:5115–5123

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  28. Cepeda C, Hurst RS, Calvert CR et al (2003) Transient and progressive electrophysiological alterations in the corticostriatal pathway in a mouse model of Huntington’s disease. J Neurosci 23:961–969

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  29. Rattray I, Smith E, Gale R et al (2013) Correlations of behavioral deficits with brain pathology assessed through longitudinal MRI and histopathology in the R6/2 mouse model of HD. PLoS One 8:e60012

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  30. Cha JH, Kosinski CM, Kerner JA et al (1998) Altered brain neurotransmitter receptors in transgenic mice expressing a portion of an abnormal human huntington disease gene. Proc Natl Acad Sci U S A 95:6480–6485

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  31. Luthi-Carter R, Strand A, Peters NL et al (2000) Decreased expression of striatal signaling genes in a mouse model of Huntington’s disease. Hum Mol Genet 9:1259–1271

    Article  PubMed  CAS  Google Scholar 

  32. Benn CL, Fox H, Bates GP (2008) Optimisation of region-specific reference gene selection and relative gene expression analysis methods for pre-clinical trials of Huntington’s disease. Mol Neurodegener 3:17

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  33. Bibb JA, Yan Z, Svenningsson P, Snyder GL et al (2000) Severe deficiencies in dopamine signaling in presymptomatic Huntington’s disease mice. Proc Natl Acad Sci U S A 97:6809–6814

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  34. Menalled L, Zanjani H, MacKenzie L et al (2000) Decrease in striatal enkephalin mRNA in mouse models of Huntington’s disease. Exp Neurol 162:328–342

    Article  PubMed  CAS  Google Scholar 

  35. Mielcarek M, Inuabasi L, Bondulich MK et al (2014) Dysfunction of the CNS-heart axis in mouse models of Huntington’s disease. PLoS Genet 10:e1004550

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  36. Ribchester RR, Thomson D, Wood NI et al (2004) Progressive abnormalities in skeletal muscle and neuromuscular junctions of transgenic mice expressing the Huntington’s disease mutation. Eur J Neurosci 20:3092–3114

    Article  PubMed  Google Scholar 

  37. Harper SQ, Staber PD, He X et al (2005) RNA interference improves motor and neuropathological abnormalities in a Huntington’s disease mouse model. Proc Natl Acad Sci U S A 102:5820–5825

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  38. Pouladi MA, Stanek LM, Xie YY et al (2012) Marked differences in neurochemistry and aggregates despite similar behavioural and neuropathological features of Huntington disease in the full-length BACHD and YAC128 mice. Hum Mol Genet 21:2219–2232

    Article  PubMed  CAS  Google Scholar 

  39. Slow EJ, van Raamsdonk J, Rogers D et al (2003) Selective striatal neuronal loss in a YAC128 mouse model of Huntington disease. Hum Mol Genet 12:1555–1567

    Article  PubMed  CAS  Google Scholar 

  40. Van Raamsdonk JM, Murphy Z, Slow EJ et al (2005) Selective degeneration and nuclear localization of mutant huntingtin in the YAC128 mouse model of Huntington disease. Hum Mol Genet 14:3823–3835

    Article  PubMed  Google Scholar 

  41. Brooks S, Higgs G, Janghra N et al (2012) Longitudinal analysis of the behavioural phenotype in YAC128 (C57BL/6J) Huntington’s disease transgenic mice. Brain Res Bull 88:113–120

    Article  PubMed  Google Scholar 

  42. Brooks SP, Jones L, Dunnett SB (2012) Longitudinal analyses of operant performance on the serial implicit learning task (SILT) in the YAC128 Huntington’s disease mouse line. Brain Res Bull 88:130–136

    Article  PubMed  Google Scholar 

  43. Brooks SP, Janghra N, Higgs GV et al (2012) Selective cognitive impairment in the YAC128 Huntington’s disease mouse. Brain Res Bull 88:121–129

    Article  PubMed  Google Scholar 

  44. Bayram-Weston Z, Jones L, Dunnett SB, Brooks SP (2012) Light and electron microscopic characterization of the evolution of cellular pathology in YAC128 Huntington's disease transgenic mice. Brain Res Bull 88:137–147

    Article  PubMed  Google Scholar 

  45. Spampanato J, Gu X, Yang XW, Mody I (2008) Progressive synaptic pathology of motor cortical neurons in a BAC transgenic mouse model of Huntington’s disease. Neuroscience 157:606–620

    Article  PubMed  CAS  Google Scholar 

  46. Hult Lundh S, Nilsson N, Soylu R et al (2013) Hypothalamic expression of mutant huntingtin contributes to the development of depressive-like behavior in the BAC transgenic mouse model of Huntington’s disease. Hum Mol Genet 22:3485–3497

    Article  PubMed  CAS  Google Scholar 

  47. Kennedy L, Evans E, Chen CM et al (2003) Dramatic tissue-specific mutation length increases are an early molecular event in Huntington disease pathogenesis. Hum Mol Genet 12:3359–3367

    Article  PubMed  CAS  Google Scholar 

  48. Pouladi MA, Xie Y, Skotte NH et al (2010) Full-length huntingtin levels modulate body weight by influencing insulin-like growth factor 1 expression. Hum Mol Genet 19:1528–1538

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  49. Kudwa AE, Menalled LB, Oakeshott S et al (2013) Increased body weight of the BAC HD transgenic mouse model of Huntington’s disease accounts for some but not all of the observed HD-like motor deficits. PLoS Curr HD 5:0ab4f3645aff523c56ecc8ccbe41a198

    Google Scholar 

  50. Menalled LB, Sison JD, Dragatsis I et al (2003) Time course of early motor and neuropathological anomalies in a knock-in mouse model of Huntington’s disease with 140 CAG repeats. J Comp Neurol 465:11–26

    Article  PubMed  CAS  Google Scholar 

  51. Heikkinen T, Lehtimaki K, Vartiainen N et al (2012) Characterization of neurophysiological and behavioral changes, MRI brain volumetry and 1H MRS in zQ175 knock-in mouse model of Huntington’s disease. PLoS One 7:e50717

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  52. Menalled LB, Kudwa AE, Miller S et al (2012) Comprehensive behavioral and molecular characterization of a new knock-in mouse model of Huntington’s disease: zQ175. PLoS One 7:e50717

    Article  CAS  Google Scholar 

  53. Wheeler VC, Auerbach W, White JK et al (1999) Length-dependent gametic CAG repeat instability in the Huntington’s disease knock-in mouse. Hum Mol Genet 8:115–122

    Article  PubMed  CAS  Google Scholar 

  54. Wheeler VC, White JK, Gutekunst CA et al (2000) Long glutamine tracts cause nuclear localization of a novel form of huntingtin in medium spiny striatal neurons in HdhQ92 and HdhQ111 knock-in mice. Hum Mol Genet 9:503–513

    Article  PubMed  CAS  Google Scholar 

  55. Trueman RC, Brooks SP, Jones L, Dunnett SB (2008) Time course of choice reaction time deficits in the Hdh(Q92) knock-in mouse model of Huntington’s disease in the operant Serial Implicit Learning Task (SILT). Behav Brain Res 189:317–324

    Article  PubMed  Google Scholar 

  56. Lin CH, Tallaksen-Greene S, Chien WM et al (2001) Neurological abnormalities in a knock-in mouse model of Huntington’s disease. Hum Mol Genet 10:137–144

    Article  PubMed  CAS  Google Scholar 

  57. Woodman B, Butler R, Landles C et al (2007) The Hdh(Q150/Q150) knock-in mouse model of HD and the R6/2 exon 1 model develop comparable and widespread molecular phenotypes. Brain Res Bull 72:83–97

    Article  PubMed  CAS  Google Scholar 

  58. Heng MY, Tallaksen-Greene SJ, Detloff PJ, Albin RL (2007) Longitudinal evaluation of the Hdh(CAG)150 knock-in murine model of Huntington’s disease. J Neurosci 27:8989–8998

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  59. Heng MY, Detloff PJ, Paulson HL, Albin RL (2010) Early alterations of autophagy in Huntington disease-like mice. Autophagy 6:1206–1208

    Article  PubMed  PubMed Central  Google Scholar 

  60. Menalled L, Lutz C, Ramboz S et al (2014) A field guide to working with mouse models of Huntington’s disease. Psychogenics Inc., The Jackson Laboratory, CHDI Foundation, New York

    Google Scholar 

  61. Brooks SP, Betteridge H, Trueman RC et al (2006) Selective extra-dimensional set shifting deficit in a knock-in mouse model of Huntington’s disease. Brain Res Bull 69:452–457

    Article  PubMed  CAS  Google Scholar 

  62. Rattray I, Smith EJ, Crum WR et al (2017) Correlations of behavioral deficits with brain pathology assessed through longitudinal MRI and histopathology in the HdhQ150/Q150 mouse model of Huntington’s disease. PLoS One 12:e0168556

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  63. Kuhn A, Goldstein DR, Hodges A et al (2007) Mutant huntingtin’s effects on striatal gene expression in mice recapitulate changes observed in human Huntington’s disease brain and do not differ with mutant huntingtin length or wild-type huntingtin dosage. Hum Mol Genet 16(15):1845–1861

    Article  PubMed  CAS  Google Scholar 

  64. Mielcarek M, Toczek M, Smeets CJ et al (2015) HDAC4-myogenin axis as an important marker of HD-related skeletal muscle atrophy. PLoS Genet 11:e1005021

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  65. Bayram-Weston Z, Torres EM, Jones L et al (2012) Light and electron microscopic characterization of the evolution of cellular pathology in the Hdh(CAG)150 Huntington’s disease knock-in mouse. Brain Res Bull 88:189–198

    Article  PubMed  Google Scholar 

  66. Tallaksen-Greene SJ, Crouse AB, Hunter JM et al (2005) Neuronal intranuclear inclusions and neuropil aggregates in HdhCAG(150) knock-in mice. Neuroscience 131:843–852

    Article  PubMed  CAS  Google Scholar 

  67. Lloret A, Dragileva E, Teed A et al (2006) Genetic background modifies nuclear mutant huntingtin accumulation and HD CAG repeat instability in Huntington’s disease knock-in mice. Hum Mol Genet 15:2015–2024

    Article  PubMed  CAS  Google Scholar 

  68. Levine MS, Klapstein GJ, Koppel A et al (1999) Enhanced sensitivity to N-methyl-d-aspartate receptor activation in transgenic and knock-in mouse models of Huntington’s disease. J Neurosci Res 58:515–532

    Article  PubMed  CAS  Google Scholar 

  69. Peng Q, Wu B, Jiang M et al (2016) Characterization of behavioral, neuropathological, brain metabolic and key molecular changes in zQ175 knock-in mouse model of Huntington’s disease. PLoS One 11:e0148839

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  70. Bradford J, Shin JY, Roberts M et al (2009) Expression of mutant huntingtin in mouse brain astrocytes causes age-dependent neurological symptoms. Proc Natl Acad Sci U S A 106:22480–22485

    Article  PubMed  PubMed Central  Google Scholar 

  71. Tebbenkamp AT, Swing D, Tessarollo L, Borchelt DR (2011) Premature death and neurologic abnormalities in transgenic mice expressing a mutant huntingtin exon-2 fragment. Hum Mol Genet 20:1633–1642

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  72. Tebbenkamp AT, Green C, Xu G et al (2011) Transgenic mice expressing caspase-6-derived N-terminal fragments of mutant huntingtin develop neurologic abnormalities with predominant cytoplasmic inclusion pathology composed largely of a smaller proteolytic derivative. Hum Mol Genet 20:2770–2782

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  73. Yamamoto A, Lucas JJ, Hen R (2000) Reversal of neuropathology and motor dysfunction in a conditional model of Huntington’s disease. Cell 101:57–66

    Article  PubMed  CAS  Google Scholar 

  74. Slow EJ, Graham RK, Osmand AP et al (2005) Absence of behavioral abnormalities and neurodegeneration in vivo despite widespread neuronal huntingtin inclusions. Proc Natl Acad Sci U S A 102:11402–11407

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  75. Gu X, Li C, Wei W, Lo V et al (2005) Pathological cell-cell interactions elicited by a neuropathogenic form of mutant Huntingtin contribute to cortical pathogenesis in HD mice. Neuron 46:433–444

    Article  PubMed  CAS  Google Scholar 

  76. Gu X, Greiner ER, Mishra R et al (2009) Serines 13 and 16 are critical determinants of full-length human mutant huntingtin induced disease pathogenesis in HD mice. Neuron 64:828–840

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  77. Tanaka Y, Igarashi S, Nakamura M et al (2006) Progressive phenotype and nuclear accumulation of an amino-terminal cleavage fragment in a transgenic mouse model with inducible expression of full-length mutant huntingtin. Neurobiol Dis 21:381–391

    Article  PubMed  CAS  Google Scholar 

  78. Martin-Aparicio E, Yamamoto A, Hernandez F et al (2001) Proteasomal-dependent aggregate reversal and absence of cell death in a conditional mouse model of Huntington’s disease. J Neurosci 21:8772–8781

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  79. Gray M, Gu X, Shirasaki DI, Cepeda C et al (2008) Cortical control of striatal pathogenesis in the Cre/LoxP conditional BAC transgenic mouse model of Huntington’s disease (BACHD). Society for Neuroscience, Washington, DC

    Google Scholar 

  80. Gu X, Andre VM, Cepeda C et al (2007) Pathological cell-cell interactions are necessary for striatal pathogenesis in a conditional mouse model of Huntington’s disease. Mol Neurodegener 2:8

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  81. Kim SH, Thomas CA, Andre VM et al (2011) Forebrain striatal-specific expression of mutant huntingtin protein in vivo induces cell-autonomous age-dependent alterations in sensitivity to excitotoxicity and mitochondrial function. ASN Neuro 3:e00060

    Article  PubMed  CAS  Google Scholar 

  82. Bradford J, Shin JY, Roberts M et al (2010) Mutant huntingtin in glial cells exacerbates neurological symptoms of Huntington disease mice. J Biol Chem 285:10653–10661

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  83. Saudou F, Finkbeiner S, Devys D, Greenberg ME (1998) Huntingtin acts in the nucleus to induce apoptosis but death does not correlate with the formation of intranuclear inclusions. Cell 95:55–66

    Article  PubMed  CAS  Google Scholar 

  84. Schilling G, Savonenko AV, Klevytska A et al (2004) Nuclear-targeting of mutant huntingtin fragments produces Huntington’s disease-like phenotypes in transgenic mice. Hum Mol Genet 13:1599–1610

    Article  PubMed  CAS  Google Scholar 

  85. Benn CL, Landles C, Li H et al (2005) Contribution of nuclear and extranuclear polyQ to neurological phenotypes in mouse models of Huntington’s disease. Hum Mol Genet 14:3065–3078

    Article  PubMed  CAS  Google Scholar 

  86. Cornett J, Cao F, Wang CE et al (2005) Polyglutamine expansion of huntingtin impairs its nuclear export. Nat Genet 37:198–204

    Article  PubMed  CAS  Google Scholar 

  87. Gu X, Cantle JP, Greiner ER et al (2015) N17 modifies mutant Huntingtin nuclear pathogenesis and severity of disease in HD BAC transgenic mice. Neuron 85:726–741

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  88. Graham RK, Deng Y, Slow EJ et al (2006) Cleavage at the caspase-6 site is required for neuronal dysfunction and degeneration due to mutant huntingtin. Cell 125:1179–1191

    Article  PubMed  CAS  Google Scholar 

  89. Waldron-Roby E, Ratovitski T, Wang X (2012) Transgenic mouse model expressing the caspase 6 fragment of mutant huntingtin. J Neurosci 32:183–193

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  90. Gafni J, Papanikolaou T, Degiacomo F et al (2012) Caspase-6 activity in a BACHD mouse modulates steady-state levels of mutant huntingtin protein but is not necessary for production of a 586 amino acid proteolytic fragment. J Neurosci 32:7454–7465

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  91. Landles C, Weiss A, Franklin S et al (2012) Caspase-6 does not contribute to the proteolysis of mutant huntingtin in the HdhQ150 knock-in mouse model of Huntington’s disease. PLoS Curr HD 4:e4fd085bfc9973

    Article  PubMed  PubMed Central  Google Scholar 

  92. Wang CE, Tydlacka S, Orr AL et al (2008) Accumulation of N-terminal mutant huntingtin in mouse and monkey models implicated as a pathogenic mechanism in Huntington’s disease. Hum Mol Genet 17:2738–2751

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  93. O’Brien R, DeGiacomo F, Holcomb J et al (2015) Integration-independent transgenic Huntington disease fragment mouse models reveal distinct phenotypes and life span in vivo. J Biol Chem 290:19287–19306

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  94. Zheng S, Clabough EB, Sarkar S et al (2010) Deletion of the huntingtin polyglutamine stretch enhances neuronal autophagy and longevity in mice. PLoS Genet 6:e1000838

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  95. Andre EA, Braatz EM, Liu JP, Zeitlin SO (2017) Generation and characterization of knock-in mouse models expressing versions of huntingtin with either an N17 or a combined polyQ and proline-rich region deletion. J Huntingtons Dis 6:47–62

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  96. Thompson LM, Aiken CT, Kaltenbach LS et al (2009) IKK phosphorylates Huntingtin and targets it for degradation by the proteasome and lysosome. J Cell Biol 187:1083–1099

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  97. Ison JR, Allen PD, O’Neill WE (2007) Age-related hearing loss in C57BL/6J mice has both frequency-specific and non-frequency-specific components that produce a hyperacusis-like exaggeration of the acoustic startle reflex. J Assoc Res Otolaryngol 8:539–550

    Article  PubMed  PubMed Central  Google Scholar 

  98. Silva AJ, Simpson EM, Takahashi JS et al (1997) Mutant mice and neuroscience: recommendations concerning genetic background. Neuron 19:755–759

    Article  Google Scholar 

  99. Farley SJ, McKay BM, Disterhoft JF, Weiss C (2011) Reevaluating hippocampus-dependent learning in FVB/N mice. Behav Neurosci 125:871

    Article  PubMed  PubMed Central  Google Scholar 

  100. Menalled L, El-Khodor BF, Hornberger M et al (2012) Effect of the rd1 mutation on motor performance in R6/2 and wild type mice. PLoS Curr HD 4:RRN1303

    Article  PubMed  PubMed Central  Google Scholar 

  101. van Dellen A, Blakemore C, Deacon R et al (2000) Delaying the onset of Huntington’s in mice. Nature 404:721–722

    Article  PubMed  Google Scholar 

  102. van Praag H, Kempermann G, Gage FH (2000) Neural consequences of enviromental enrichment. Nat Rev Neurosci 1:191–198

    Article  PubMed  CAS  Google Scholar 

  103. Hockly E, Cordery PM, Woodman B et al (2002) Environmental enrichment slows disease progression in R61/2 Huntington’s disease mice. Ann Neurol 51:235–242

    Article  PubMed  Google Scholar 

  104. Skillings EA, Wood NI, Morton AJ (2014) Beneficial effects of environmental enrichment and food entrainment in the R6/2 mouse model of Huntington’s disease. Brain Behav 4:675–686

    Article  PubMed  PubMed Central  Google Scholar 

  105. Carter RJ, Hunt MJ, Morton AJ (2000) Environmental stimulation increases survival in mice transgenic for exon 1 of the Huntington’s disease gene. Mov Disord 15:925–937

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

G.B. is supported by grants from the CHDI Foundation, the Medical Research Council and Wellcome Trust.

Author information

Authors and Affiliations

  1. Department of Neurodegenerative Disease, Huntington’s Disease Centre and Dementia Research Institute, University College London Institute of Neurology, London, WC1N 3BG, UK

    Pamela P. Farshim & Gillian P. Bates

Authors
  1. Pamela P. Farshim
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Gillian P. Bates
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Gillian P. Bates .

Editor information

Editors and Affiliations

  1. Brain Repair Group, Cardiff University, Cardiff, United Kingdom

    Sophie V. Precious

  2. Brain Repair Group, Cardiff University, Cardiff, United Kingdom

    Anne E. Rosser

  3. Brain Repair Group, Cardiff University, Cardiff, United Kingdom

    Stephen B. Dunnett

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer Science+Business Media, LLC, part of Springer Nature

About this protocol

Check for updates. Verify currency and authenticity via CrossMark

Cite this protocol

Farshim, P.P., Bates, G.P. (2018). Mouse Models of Huntington’s Disease. In: Precious, S., Rosser, A., Dunnett, S. (eds) Huntington’s Disease. Methods in Molecular Biology, vol 1780. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-7825-0_6

Download citation

  • DOI: https://doi.org/10.1007/978-1-4939-7825-0_6

  • Published:

  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-7824-3

  • Online ISBN: 978-1-4939-7825-0

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics

Search

Navigation