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- Description
- Phenotype
- Genes & alleles
- Genotyping
- Health & husbandry
- References
- Purchasing information
- Terms of Use
Description
Strain Information
Type Coisogenic; Mutant Strain; Transgenic; Additional information on Genetically Engineered Mutant Mice. Mating System Noncarrier x Hemizygote (Female x Male) Species laboratory mouse Donating Investigator Michael Hayden, University of British Columbia Description
These transgenic mice express the human huntingtin protein containing a 133 CAG repeat expansion and a mutation in exon 13 conferring resistance to caspase-6 cleavage to the gene product. Expected caspase-6 cleaved fragments are not detected in brain lysates by Western blot analysis. Transgenic mice have brain weight and striatal volume similar to wildtype controls and do not exhibit neuronal loss at 12 months of age when compared to transgenic mice that express human huntingtin protein containing a 128 CAG repeat (FVB-Tg(YAC128)53Hay/J Stock No. 004938). These transgenic mice have activity levels and motor function similar to wildtype controls, and are resistant to neuron excitotoxicity. Immunohistochemical analysis of striatal brain sections reveals delayed nuclear localization of mutant huntingtin protein in these transgenic mice at nine months of age. Between nine and 12 months of age, an increase of nuclear huntingtin is observed. Homozygotes are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. This mutant mouse strain represents a model that may be useful in studies of Huntington?s disease. This strain can serve as the control for the FVB-Tg(YAC128)53Hay/J (Stock No. 004938).Development
A YAC containing a full-length human huntingtin gene was modified with a 133 CAG repeat expansion in exon 1 and a mutation in exon 13, at position 586, which encodes the caspase-6 cleavage site. The resulting construct (YAC353G6) was injected into FVB/NJ pronuclei. Founder line W7 (C6R7) was subsequently established. The mice were then backcrossed to FVB/NJ for 17 generations before arriving at The Jackson Laboratory.
Control Information
| Control | ||
|---|---|---|
| Noncarrier | ||
| 001800 FVB/NJ | ||
| Considerations for Choosing Controls | ||
Related Strains
Strains carrying other alleles of HTT
006471 B6.Cg-Tg(HDexon1)61Gpb/J 004360 B6;SJL-Tg(HD)63Aron/J 003627 B6C3-Tg(HD82Gln)81Dbo/J 002809 B6CBA-Tg(HDexon1)61Gpb/1J 002810 B6CBA-Tg(HDexon1)62Gpb/1J 006494 B6CBA-Tg(HDexon1)62Gpb/3J 007578 CBy.Cg-Tg(HDexon1)61Gpb/J 004938 FVB-Tg(YAC128)53Hay/J 008197 FVB/N-Tg(HTT*97Q)IXwy/J 003640 FVB/NJ-Tg(YAC72)2511Hay/J View Strains carrying other alleles of HTT (10 strains)
Phenotype
Phenotype Information
assigned by genotype
Tg(YAC353G6)W7Hay/0
FVB/NJ-Tg(YAC353G6)W7Hay
- nervous system phenotype
- *normal* nervous system phenotype (MGI Ref ID J:120991)
- transgenic mice show no neuronal loss or neuronal excitoxicity compared to wild-type controls, and in contrast to Tg(YAC128)53Hay mice at 12 months of age
- mice perform as well as wild-type mice in rotarod tests up to and including 10 months, and perform better than Tg(YAC128)53Hay mice at 2, 6, and 8 months
- mice perform better than Tg(YAC128)53Hay mice in open field tests at 2, 6, 8, and 10 months and are indistinguishable from wild-type controls, displaying no hypokinesia
- abnormal striatum morphology (MGI Ref ID J:120991)
- increased volume compared to Tg(YAC128)53Hay mice at 18 months
- striatal volume is indistinguishable from wild-type
- nuclear localization of htt in striatum at 9 months is just detectable, similar to Tg(YAC128)53Hay mice at 2 months of age and this increases with age such that at 12 months,
- increased brain weight (MGI Ref ID J:120991)
- increased compared to Tg(YAC128)53Hay mice at 18 months
- brain weight is indistinguishable from wild-type
Tg(YAC353G6)W7Hay/Tg(YAC353G6)W7Hay
FVB/NJ-Tg(YAC353G6)W7Hay
- nervous system phenotype
- decreased susceptibility to neuronal excitotoxicity (MGI Ref ID J:120991)
- cultured medium spiny neurons are resistant to NMDAR-mediated excitotoxicity compared to wild-type (2.4% apoptotic cells vs 8.6% in wild-type cultures)
- in vivo, quinolinic acid-induced lesion volume is less than that observed in wild-type mice
- medium spiny neurons exposed to staurosporine show less cell death than wild-type neurons in culture (20% apoptotic cells vs 36.8% in wild-type cultures)
- homeostasis/metabolism phenotype
- decreased susceptibility to neuronal excitotoxicity (MGI Ref ID J:120991)
- cultured medium spiny neurons are resistant to NMDAR-mediated excitotoxicity compared to wild-type (2.4% apoptotic cells vs 8.6% in wild-type cultures)
- in vivo, quinolinic acid-induced lesion volume is less than that observed in wild-type mice
- medium spiny neurons exposed to staurosporine show less cell death than wild-type neurons in culture (20% apoptotic cells vs 36.8% in wild-type cultures)
This mouse can be used to support research in many areas including:
HTT relatedNeurobiology Research
Huntington's disease
Developmental Biology Research
Neurodevelopmental Defects
Mouse/Human Gene Homologs
Huntington's disease (chorea)
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
| Allele Symbol | Tg(YAC353G6)W7Hay | ||
|---|---|---|---|
| Allele Name | transgene insertion W7, Michael Hayden | ||
| Allele Type | Transgenic (random, expressed) | ||
| Common Name(s) | C6R7; YAC353G6; | ||
| Strain of Origin | FVB/NJ | ||
| Expressed Gene | HTT, huntingtin, human | ||
| Promoter | HTT, huntingtin, human | ||
| Molecular Note | A YAC containing a full-length human huntingtin gene was modified with a 133 CAG repeat expansion in exon 1 and a mutation in exon 13, at position 586, which encodes the caspase-6 cleavage site. Founder line W7 (C6R7) was subsequently established. Caspase-6 cleavage products are not detected in brain lysates by Western blot. [MGI Ref ID J:120991] | ||
Genotyping
Genotyping Information
This strain will not have a genotyping protocol or one is not currently available.
Helpful Links
Optimizing PCR Protocols
References
References
Selected Reference(s)
Graham RK; Deng Y; Slow EJ; Haigh B; Bissada N; Lu G; Pearson J; Shehadeh J; Bertram L; Murphy Z; Warby SC; Doty CN; Roy S; Wellington CL; Leavitt BR; Raymond LA; Nicholson DW; Hayden MR. 2006. Cleavage at the caspase-6 site is required for neuronal dysfunction and degeneration due to mutant huntingtin. Cell 125(6):1179-91. [PubMed: 16777606] [MGI Ref ID J:120991]
Additional References
Tg(YAC353G6)W7Hay relatedWang CE; Tydlacka S; Orr AL; Yang SH; Graham RK; Hayden MR; Li S; Chan AW; Li XJ. 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(17):2738-51. [PubMed: 18558632] [MGI Ref ID J:138148]
Health & husbandry
Health & Colony Maintenance Information
Animal Health Reports
Room Number AX12
Colony Maintenance
Breeding & Husbandry When maintaining a live colony, these mice are bred as homozygotes. To maintain the 133 CAG repeat, the donating investigator generates hemizygotes to re-establish the homozygous colony every 3rd generation. Mating System Noncarrier x Hemizygote (Female x Male) Diet Information LabDiet® 5K52/5K67
Purchasing information
Pricing, Supply Level & Notes, Controls, General Terms & Conditions
Pricing
| Pricing for USA, Canada and Mexico shipping destinations |
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Weeks of Age Price* Gender Genotypes Provided Individual Mouse Price $52.50 Female or Male Hemizygous for Tg(YAC353G6)W7Hay *Price(s) in US dollars ($)
Pairs /Price* Pair Genotype $288.65 Hemizygous for Tg(YAC353G6)W7Hay x Noncarrier $288.65 Noncarrier x Hemizygous for Tg(YAC353G6)W7Hay
Additional Supply Details
| Supply Notes |
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| Pricing for International shipping destinations |
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Weeks of Age Price* Gender Genotypes Provided Individual Mouse Price $68.30 Female or Male Hemizygous for Tg(YAC353G6)W7Hay *Price(s) in US dollars ($)
Pairs /Price* Pair Genotype $375.30 Hemizygous for Tg(YAC353G6)W7Hay x Noncarrier $375.30 Noncarrier x Hemizygous for Tg(YAC353G6)W7Hay
Additional Supply Details
| Supply Notes |
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Supply Details
| Standard Supply | Repository-Live. A collection of over 1000 strains maintained as live colonies. Individual colonies are sized to meet current customer demand. Delivery for orders of 10 mice or less ranges on average from one to eight weeks; mice are generally shipped between four to six weeks of age with a maximum shipping age of ~nine weeks. Colony sizes do not generally support stringent age specifications for large volumes of mice; however custom orders and larger quantities of mice are easily arranged. Estimated ship dates for all orders provided within 48 hours of order placement. |
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Control Information
| Control | ||
|---|---|---|
| Noncarrier | ||
| 001800 FVB/NJ | ||
| Considerations for Choosing Controls | ||
| USA, Canada and Mexico - Control Pricing Information for Genetically Engineered Mutant Strains. | ||
| International - Control Pricing Information for Genetically Engineered Mutant Strains. | ||
General Terms and Conditions
See Terms of Use
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The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project.Ordering and Purchasing Information
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