Strain Name:

FVB/NJ-Tg(YAC72)2511Hay/J

Stock Number:

003640

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Description

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Strain Information

Type Mutant Strain; Transgenic;
Additional information on Genetically Engineered and Mutant Mice.
Visit our online Nomenclature tutorial.
Specieslaboratory mouse
 
Donating Investigator Michael R Hayden,   University of British Columbia

Description
Mice homozygous for this transgene are viable and fertile. The human huntingtin transgenic protein is expressed widely in many tissues (identical to the endogenous huntingtin protein), but has highest levels of expression in the brain and testes. Electrophysiological abnormalities can be measured by six months. A behavioral phenotype is first detected at seven months when evidence of mild hyperkinetic movement disorder is noticeable. This disorder is characterized by progressive spontaneous hyperactivity during the dark phase of open field-testing. By 12 months of age selective degeneration of medium spiny neurons in the lateral striatum is observed. This degeneration is associated with the translocation of N-terminal huntingtin fragments to the nucleus. This strain represents a Huntington's Disease mouse model where a mutant full-length human huntingtin is expressed under control of its endogenous promoter.

Development
A YAC containing a full-length human huntingtin gene was modified with a 72 CAG repeat expansion in exon 1. The resulting construct (YAC72) was injected into FVB/N pronuclei.

Control Information

  Control
   Noncarrier
   001800 FVB/NJ
 
  Considerations for Choosing Controls

Related Strains

View Huntington's Disease Models     (29 strains)

View Strains carrying other alleles of HTT     (14 strains)

Additional Web Information

Visit our Huntington's Disease page for a full listing of Huntington's strains and research services.

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI
- Characteristics of this human disease are associated with transgenes and other mutation types in the mouse.
Huntington Disease; HD
View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

Tg(YAC72)2511Hay/0

        involves: FVB/N
  • reproductive system phenotype
  • *normal* reproductive system phenotype
    • mice exhibit normal testes and are fertile   (MGI Ref ID J:67366)
  • nervous system phenotype
  • increased susceptibility to neuronal excitotoxicity
    • NMDA or glutamate receptor-mediated   (MGI Ref ID J:144917)
  • cellular phenotype
  • increased susceptibility to neuronal excitotoxicity
    • NMDA or glutamate receptor-mediated   (MGI Ref ID J:144917)
  • homeostasis/metabolism phenotype
  • increased susceptibility to neuronal excitotoxicity
    • NMDA or glutamate receptor-mediated   (MGI Ref ID J:144917)

Tg(YAC72)2511Hay/?

        involves: FVB/N
  • nervous system phenotype
  • abnormal excitatory postsynaptic potential
    • hippocampal slices from 6 month old mice display a hyperexcitability exhibited as a broad EPSP at the distal dendrites   (MGI Ref ID J:55405)
  • abnormal long term potentiation
    • following tetanization most slices from 6 month old mice exhibit a greater short-term potentiation when compared to controls   (MGI Ref ID J:55405)
    • reduced long term potentiation
      • by 10 months of age, LTP is not induced in CA1 neurons; high frequency stimulation induces depression instead of potentiation   (MGI Ref ID J:55405)
  • abnormal striatum morphology
    • nuclear translocation of the N-terminal portion of HD is observed in striatal neurons of 12 month old mice with an immunoreactive antibody (EM48)   (MGI Ref ID J:55405)
  • enhanced NMDA-mediated synaptic currents
    • fast synaptic response in these mice has a prominent NMDA component   (MGI Ref ID J:55405)
  • neuron degeneration
    • selective degeneration is observed in the striatum at 12 months of age   (MGI Ref ID J:55405)
    • neurons are shrunken and hyperchromatic   (MGI Ref ID J:55405)
  • behavior/neurological phenotype
  • hyperactivity
    • progressive hyperactivity is observed in the dark phase of open field testing beginning at 7 months of age   (MGI Ref ID J:55405)
  • unidirectional circling
    • circling was observed in one mouse at 8.5 months of age   (MGI Ref ID J:55405)

Tg(YAC72)2511Hay/Tg(YAC72)2511Hay

        FVB/N-Tg(YAC72)2511Hay
  • nervous system phenotype
  • increased neuron apoptosis
    • general increase in stress-induced apoptosis in primary cultures of striatal neurons   (MGI Ref ID J:105728)
    • in cultured striatal medium spiny neurons in response to mitochondria stress   (MGI Ref ID J:105728)
    • increased susceptibility to neuronal excitotoxicity
      • in cultured striatal medium spiny neurons following exposure to NMDA, the Ca2+ ionophore A23187, or KCl plus the L-type calcium channel agonist FPL 64176   (MGI Ref ID J:105728)
      • apoptosis induced by KCl alone is less than in mice homozygous for Tg(YAC128)55Hay   (MGI Ref ID J:105728)
  • homeostasis/metabolism phenotype
  • increased susceptibility to neuronal excitotoxicity
    • in cultured striatal medium spiny neurons following exposure to NMDA, the Ca2+ ionophore A23187, or KCl plus the L-type calcium channel agonist FPL 64176   (MGI Ref ID J:105728)
    • apoptosis induced by KCl alone is less than in mice homozygous for Tg(YAC128)55Hay   (MGI Ref ID J:105728)
  • cellular phenotype
  • increased neuron apoptosis
    • general increase in stress-induced apoptosis in primary cultures of striatal neurons   (MGI Ref ID J:105728)
    • in cultured striatal medium spiny neurons in response to mitochondria stress   (MGI Ref ID J:105728)
    • increased susceptibility to neuronal excitotoxicity
      • in cultured striatal medium spiny neurons following exposure to NMDA, the Ca2+ ionophore A23187, or KCl plus the L-type calcium channel agonist FPL 64176   (MGI Ref ID J:105728)
      • apoptosis induced by KCl alone is less than in mice homozygous for Tg(YAC128)55Hay   (MGI Ref ID J:105728)
View Research Applications

Research Applications
This mouse can be used to support research in many areas including:

HTT related

Developmental Biology Research
Neurodevelopmental Defects

Neurobiology Research
Ataxia (Movement) Defects
Behavioral and Learning Defects
Cortical Defects
Huntington's disease
Neurodegeneration
Neurodevelopmental Defects
Neurotransmitter Receptor and Synaptic Vesicle Defects
Tremor Defects

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Tg(YAC72)2511Hay
Allele Name transgene insertion 2511, Michael Hayden
Allele Type Transgenic (random, expressed)
Common Name(s) YAC72;
Mutation Made By J. Hodgson,   University of British Columbia
Strain of OriginFVB/N
Expressed Gene HTT, huntingtin, human
Promoter HTT, huntingtin, human
General Note Homozygous transgenic mice are viable and fertile. In these mice the human huntingtin transgenic protein is expressed widely in many tissues (identical to the endogenous huntingtin protein), with highest expression levels in the brain and testes. Electrophysiological abnormalities can be measured by 6 months. A behavioral phenotype is first detected at 7 months when evidence of mild hyperkinetic movement disorder is noticeable. This disorder is characterized by progressive spontaneous hyperactivity during the dark phase of open field-testing. By 12 months of age selective degeneration of medium spiny neurons in the lateral striatum is observed. This degeneration is associated with the translocation of N-terminal huntingtin fragments to the nucleus.
Molecular Note A YAC containing a full-length human huntingtin gene was modified with a 72 CAG repeat expansion in exon 1. The resulting construct (YAC72) was used to generate transgenic mice. The endogenous human HDH promoter directed expression in many tissues with levels in the brain and testes being the highest. [MGI Ref ID J:55405]
 

Genotyping

Genotyping Information

Genotyping Protocols

Tg(YAC72)2511Hay - (HDexon1), Standard PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Hodgson JG; Agopyan N; Gutekunst CA; Leavitt BR; LePiane F; Singaraja R ; Smith DJ ; Bissada N ; McCutcheon K ; Nasir J ; Jamot L ; Li XJ ; Stevens ME ; Rosemond E ; Roder JC ; Phillips AG ; Rubin EM ; Hersch SM ; Hayden MR. 1999. A YAC mouse model for Huntington's disease with full-length mutant huntingtin, cytoplasmic toxicity, and selective striatal neurodegeneration. Neuron 23(1):181-92. [PubMed: 10402204]  [MGI Ref ID J:55405]

Additional References

Fan MM; Fernandes HB; Zhang LY; Hayden MR; Raymond LA. 2007. Altered NMDA receptor trafficking in a yeast artificial chromosome transgenic mouse model of Huntington's disease. J Neurosci 27(14):3768-79. [PubMed: 17409241]  [MGI Ref ID J:119402]

Tg(YAC72)2511Hay related

Benn CL; Slow EJ; Farrell LA; Graham R; Deng Y; Hayden MR; Cha JH. 2007. Glutamate receptor abnormalities in the YAC128 transgenic mouse model of Huntington's disease. Neuroscience 147(2):354-72. [PubMed: 17544587]  [MGI Ref ID J:124041]

Cowan CM; Fan MM; Fan J; Shehadeh J; Zhang LY; Graham RK; Hayden MR; Raymond LA. 2008. Polyglutamine-modulated striatal calpain activity in YAC transgenic huntington disease mouse model: impact on NMDA receptor function and toxicity. J Neurosci 28(48):12725-35. [PubMed: 19036965]  [MGI Ref ID J:142345]

Crook ZR; Housman D. 2011. Huntington's disease: can mice lead the way to treatment? Neuron 69(3):423-35. [PubMed: 21315254]  [MGI Ref ID J:174750]

Desplats PA; Lambert JR; Thomas EA. 2008. Functional roles for the striatal-enriched transcription factor, Bcl11b, in the control of striatal gene expression and transcriptional dysregulation in Huntington's disease. Neurobiol Dis 31(3):298-308. [PubMed: 18595722]  [MGI Ref ID J:138707]

Fan J; Cowan CM; Zhang LY; Hayden MR; Raymond LA. 2009. Interaction of postsynaptic density protein-95 with NMDA receptors influences excitotoxicity in the yeast artificial chromosome mouse model of Huntington's disease. J Neurosci 29(35):10928-38. [PubMed: 19726651]  [MGI Ref ID J:152453]

Fan MM; Fernandes HB; Zhang LY; Hayden MR; Raymond LA. 2007. Altered NMDA receptor trafficking in a yeast artificial chromosome transgenic mouse model of Huntington's disease. J Neurosci 27(14):3768-79. [PubMed: 17409241]  [MGI Ref ID J:119402]

Jenkins BG; Andreassen OA; Dedeoglu A; Leavitt B; Hayden M; Borchelt D; Ross CA; Ferrante RJ; Beal MF. 2005. Effects of CAG repeat length, HTT protein length and protein context on cerebral metabolism measured using magnetic resonance spectroscopy in transgenic mouse models of Huntington's disease. J Neurochem 95(2):553-62. [PubMed: 16135087]  [MGI Ref ID J:129784]

Kuhn A; Goldstein DR; Hodges A; Strand AD; Sengstag T; Kooperberg C; Becanovic K; Pouladi MA; Sathasivam K; Cha JH; Hannan AJ; Hayden MR; Leavitt BR; Dunnett SB; Ferrante RJ; Albin R; Shelbourne P; Delorenzi M; Augood SJ; Faull RL; Olson JM; Bates GP; Jones L; Luthi-Carter R. 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):1845-61. [PubMed: 17519223]  [MGI Ref ID J:142943]

Leavitt BR; Guttman JA; Hodgson JG; Kimel GH; Singaraja R; Vogl AW; Hayden MR. 2001. Wild-type huntingtin reduces the cellular toxicity of mutant huntingtin in vivo. Am J Hum Genet 68(2):313-24. [PubMed: 11133364]  [MGI Ref ID J:67366]

Leavitt BR; van Raamsdonk JM; Shehadeh J; Fernandes H; Murphy Z; Graham RK; Wellington CL; Raymond LA; Hayden MR. 2006. Wild-type huntingtin protects neurons from excitotoxicity. J Neurochem 96(4):1121-9. [PubMed: 16417581]  [MGI Ref ID J:144917]

Li L; Fan M; Icton CD; Chen N; Leavitt BR; Hayden MR; Murphy TH; Raymond LA. 2003. Role of NR2B-type NMDA receptors in selective neurodegeneration in Huntington disease. Neurobiol Aging 24(8):1113-21. [PubMed: 14643383]  [MGI Ref ID J:127986]

Li L; Murphy TH; Hayden MR; Raymond LA. 2004. Enhanced striatal NR2B-containing N-methyl-D-aspartate receptor-mediated synaptic currents in a mouse model of Huntington disease. J Neurophysiol 92(5):2738-46. [PubMed: 15240759]  [MGI Ref ID J:134753]

Milnerwood AJ; Gladding CM; Pouladi MA; Kaufman AM; Hines RM; Boyd JD; Ko RW; Vasuta OC; Graham RK; Hayden MR; Murphy TH; Raymond LA. 2010. Early increase in extrasynaptic NMDA receptor signaling and expression contributes to phenotype onset in Huntington's disease mice. Neuron 65(2):178-90. [PubMed: 20152125]  [MGI Ref ID J:167657]

Milnerwood AJ; Raymond LA. 2007. Corticostriatal synaptic function in mouse models of Huntington's disease: early effects of huntingtin repeat length and protein load. J Physiol 585(Pt 3):817-31. [PubMed: 17947312]  [MGI Ref ID J:144266]

Seo H; Kim W; Isacson O. 2008. Compensatory changes in the ubiquitin-proteasome system, brain-derived neurotrophic factor and mitochondrial complex II/III in YAC72 and R6/2 transgenic mice partially model Huntington's disease patients. Hum Mol Genet 17(20):3144-53. [PubMed: 18640989]  [MGI Ref ID J:139795]

Shehadeh J; Fernandes HB; Zeron Mullins MM; Graham RK; Leavitt BR; Hayden MR; Raymond LA. 2006. Striatal neuronal apoptosis is preferentially enhanced by NMDA receptor activation in YAC transgenic mouse model of Huntington disease. Neurobiol Dis 21(2):392-403. [PubMed: 16165367]  [MGI Ref ID J:105728]

Van Raamsdonk JM; Gibson WT; Pearson J; Murphy Z; Lu G; Leavitt BR; Hayden MR. 2006. Body weight is modulated by levels of full-length Huntingtin. Hum Mol Genet 15(9):1513-23. [PubMed: 16571604]  [MGI Ref ID J:108220]

Weydt P; Pineda VV; Torrence AE; Libby RT; Satterfield TF; Lazarowski ER; Gilbert ML; Morton GJ; Bammler TK; Strand AD; Cui L; Beyer RP; Easley CN; Smith AC; Krainc D; Luquet S; Sweet IR; Schwartz MW; La Spada AR. 2006. Thermoregulatory and metabolic defects in Huntington's disease transgenic mice implicate PGC-1alpha in Huntington's disease neurodegeneration. Cell Metab 4(5):349-62. [PubMed: 17055784]  [MGI Ref ID J:129751]

Zeron MM; Fernandes HB; Krebs C; Shehadeh J; Wellington CL; Leavitt BR; Baimbridge KG; Hayden MR; Raymond LA. 2004. Potentiation of NMDA receptor-mediated excitotoxicity linked with intrinsic apoptotic pathway in YAC transgenic mouse model of Huntington's disease. Mol Cell Neurosci 25(3):469-79. [PubMed: 15033175]  [MGI Ref ID J:89338]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200.

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls


Pricing for USA, Canada and Mexico shipping destinations View International Pricing

Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $2450.00
Animals Provided

At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Supply Notes

  • Cryorecovery - Standard.
    Progeny testing is not required.
    The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 11 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.

    Cryorecovery to establish a Dedicated Supply for greater quantities of mice
    Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).

Pricing for International shipping destinations View USA Canada and Mexico Pricing

Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $3185.00
Animals Provided

At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Supply Notes

  • Cryorecovery - Standard.
    Progeny testing is not required.
    The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 11 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.

    Cryorecovery to establish a Dedicated Supply for greater quantities of mice
    Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).

View USA Canada and Mexico Pricing View International Pricing

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Control Information

  Control
   Noncarrier
   001800 FVB/NJ
 
  Considerations for Choosing Controls
  Control Pricing Information for Genetically Engineered Mutant Strains.
 

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