Strain Name:

STOCK Htttm4Mem/J

Stock Number:

003455

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Availability:

Cryopreserved - Ready for recovery

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

Former Names STOCK Hdtm4Mem/J    (Changed: 13-DEC-07 )
STOCK Hdhtm4Mem/J    (Changed: 19-SEP-07 )
Type Mutant Stock; Targeted Mutation;
Additional information on Genetically Engineered and Mutant Mice.
Visit our online Nomenclature tutorial.
Specieslaboratory mouse
GenerationF?+9p
Generation Definitions
 
Donating InvestigatorDr. Marcy MacDonald,   Massachusetts General Hospital

Description
This strain carries 92 CAG repeat units in the first exon of the endogenous Htt gene. Huntington's-like pathology is seen in the striatum, including nuclear localization of the protein, N-terminal inclusions, and insoluble aggregate formation. Instability of the length of the CAG repeat between generations is seen. Expression of this phenotype is delayed relative to Htttm5 (Stock No. 003456).

Control Information

  Control
   None Available
 
  Considerations for Choosing Controls

Related Strains

View Huntington's Disease Models     (28 strains)

Strains carrying   Htttm4Mem allele
003597   B6.129-Htttm4Mem/J
View Strains carrying   Htttm4Mem     (1 strain)

View Strains carrying other alleles of Htt     (12 strains)

Additional Web Information

Visit the Huntington's Diease Resource site for helpful information on Huntington's Disease and research resources.

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI
- Model with phenotypic similarity to human disease where etiologies involve orthologs. Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).
Huntington Disease; HD
View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

Htttm4Mem/Htt+

        involves: 129S1/Sv * 129X1/SvJ * CD-1
  • nervous system phenotype
  • abnormal striatum morphology   (MGI Ref ID J:60937)
    • abnormal medium spiny neuron morphology
      • exhibit relocation of the mutant protein to the nucleus in medium sized spiny neurons and much later, the formation of morphologic nuclear inclusions and insoluble aggregate that are hallmarks of Huntington's Disease in humans, although at a slower rate than seen in homozygotes   (MGI Ref ID J:60937)
  • neuronal intranuclear inclusions   (MGI Ref ID J:60937)

Htttm4Mem/Htttm4Mem

        involves: 129S1/Sv * 129X1/SvJ * CD-1
  • nervous system phenotype
  • abnormal cerebral cortex morphology
    • QUIN and 3-HK levels are increased in the cortex beginning at 15 months of age, as seen in patients with Huntington disease   (MGI Ref ID J:111237)
  • abnormal nervous system physiology
    • between 5 and 12 months of age, striatal mitochondria develops resistance to calcium, becoming equally sensitive to calcium as cortical mitochondria, whereas in wild-type, striatal mitochondria is more sensitive to calcium than cortical mitochondria   (MGI Ref ID J:99425)
  • abnormal striatum morphology
    • the levels of both the endogenous excitotoxin quinolinic acid (QUIN) and its bioprecursor, 3-hydroxykynurenine (3-HK) are increased in the striatum beginning at 15 months of age, similarly to that seen in Huntington disease patients   (MGI Ref ID J:111237)
    • abnormal medium spiny neuron morphology
      • exhibit relocation of the mutant protein to the nucleus in medium sized spiny neurons and much later, the formation of morphologic nuclear inclusions (at 12-15 months) and insoluble aggregate that are hallmarks of Huntington's Disease in humans   (MGI Ref ID J:60937)
  • neuronal intranuclear inclusions
    • observed at 12-15 months   (MGI Ref ID J:60937)
  • behavior/neurological phenotype
  • limb grasping
    • observe clasping behavior is some mutants by one year of age   (MGI Ref ID J:99425)
View Research Applications

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

Htttm4Mem related

Neurobiology Research
Cortical Defects
Huntington's disease
Neurodegeneration

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Htttm4Mem
Allele Name targeted mutation 4, Marcy E MacDonald
Allele Type Targeted (knock-in)
Common Name(s) HdhQ92; Hdhtm4Mem;
Mutation Made ByDr. Marcy MacDonald,   Massachusetts General Hospital
Strain of Origin(129X1/SvJ x 129S1/Sv)F1-Kitl<+>
ES Cell Line NameR1
ES Cell Line Strain(129X1/SvJ x 129S1/Sv)F1-Kitl<+>
Promoter Htt, huntingtin, mouse, laboratory
Molecular Note This allele carries 90 CAG repeat units, with 92 glutamines, in the first exon of the endogenous gene. [MGI Ref ID J:52440]

Genotyping

Genotyping Information

Genotyping Protocols

Htttm4Mem, Separated PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Wheeler VC; White JK; Gutekunst CA; Vrbanac V; Weaver M; Li XJ; Li SH; Yi H; Vonsattel JP; Gusella JF; Hersch S; Auerbach W; Joyner AL; MacDonald ME. 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(4):503-13. [PubMed: 10699173]  [MGI Ref ID J:60937]

Additional References

White JK; Auerbach W; Duyao MP; Vonsattel JP; Gusella JF; Joyner AL ; MacDonald ME. 1997. Huntingtin is required for neurogenesis and is not impaired by the Huntington's disease CAG expansion. Nat Genet 17(4):404-10. [PubMed: 9398841]  [MGI Ref ID J:44391]

Htttm4Mem related

Brustovetsky N; LaFrance R; Purl KJ; Brustovetsky T; Keene CD; Low WC; Dubinsky JM. 2005. Age-dependent changes in the calcium sensitivity of striatal mitochondria in mouse models of Huntington's Disease. J Neurochem 93(6):1361-70. [PubMed: 15935052]  [MGI Ref ID J:99425]

Cyr M; Sotnikova TD; Gainetdinov RR; Caron MG. 2006. Dopamine enhances motor and neuropathological consequences of polyglutamine expanded huntingtin. FASEB J 20(14):2541-3. [PubMed: 17065224]  [MGI Ref ID J:146707]

Fossale E; Wheeler VC; Vrbanac V; Lebel LA; Teed A; Mysore JS; Gusella JF; MacDonald ME; Persichetti F. 2002. Identification of a presymptomatic molecular phenotype in Hdh CAG knock-in mice. Hum Mol Genet 11(19):2233-41. [PubMed: 12217951]  [MGI Ref ID J:79126]

Guidetti P; Bates GP; Graham RK; Hayden MR; Leavitt BR; MacDonald ME; Slow EJ; Wheeler VC; Woodman B; Schwarcz R. 2006. Elevated brain 3-hydroxykynurenine and quinolinate levels in Huntington disease mice. Neurobiol Dis 23(1):190-7. [PubMed: 16697652]  [MGI Ref ID J:111237]

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]

Lynch G; Kramar EA; Rex CS; Jia Y; Chappas D; Gall CM; Simmons DA. 2007. Brain-derived neurotrophic factor restores synaptic plasticity in a knock-in mouse model of Huntington's disease J Neurosci 27(16):4424-4434. [PubMed: 17442827]  [MGI Ref ID J:119836]

Namura S; Hirt L; Wheeler VC; McGinnis KM; Hilditch-Maguire P; Moskowitz MA; MacDonald ME; Persichetti F. 2002. The HD mutation does not alter neuronal death in the striatum of Hdh(Q92) knock-in mice after mild focal ischemia. Neurobiol Dis 11(1):147-54. [PubMed: 12460554]  [MGI Ref ID J:125447]

Trueman RC; Brooks SP; Jones L; Dunnett SB. 2009. Rule learning, visuospatial function and motor performance in the Hdh(Q92) knock-in mouse model of Huntington's disease. Behav Brain Res 203(2):215-22. [PubMed: 19445966]  [MGI Ref ID J:150366]

Trueman RC; Brooks SP; Jones L; Dunnett SB. 2007. The operant serial implicit learning task reveals early onset motor learning deficits in the Hdh knock-in mouse model of Huntington's disease. Eur J Neurosci 25(2):551-8. [PubMed: 17284197]  [MGI Ref ID J:118627]

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(2):317-24. [PubMed: 18367261]  [MGI Ref ID J:133206]

Wheeler VC; Auerbach W; White JK; Srinidhi J; Auerbach A; Ryan A ; Duyao MP ; Vrbanac V ; Weaver M ; Gusella JF ; Joyner AL ; MacDonald ME. 1999. Length-dependent gametic CAG repeat instability in the Huntington's disease knock-in mouse. Hum Mol Genet 8(1):115-22. [PubMed: 9887339]  [MGI Ref ID J:52440]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

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

Colony Maintenance

Diet Information LabDiet® 5K52/5K67

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* $3175.00
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* $4127.50
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.

General Supply Notes

Control Information

  Control
   None Available
 
  Considerations for Choosing Controls
  Control Pricing Information for Genetically Engineered Mutant Strains.
 

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