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| These RosaHD mutant mice allow cre-conditional expression of the neuropathogenic mhtt-exon1 protein and may be useful in studying Huntington’s disease or other polyQ disorders. | |||||||||||||||
- Description
- Phenotype
- Genes & alleles
- Genotyping
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Description
Strain Information
Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Mating System Heterozygote x +/+ sibling (Female x Male) 01-JAN-08 Species laboratory mouse Generation N12+F4 (26-JAN-09) Donating Investigator X. William Yang, University of California Los Angeles Description
Mice heterozygous for the RosaHD mutant allele are viable and fertile. These mice have the neuropathogenic polyQ-mutant variant of the human Huntingtin protein (mhtt-exon1; 103Q) inserted into the Gt(ROSA)26Sor locus. Expression of mhtt-exon1 is blocked by an upstream loxP-flanked transcriptional STOP sequence. When bred to mice with a Cre recombinase gene under the control of a promoter of interest, the STOP sequence is deleted in the tissue of interest, and mhtt-exon1 expression is observed. As these RosaHD mutant mice allow cre-conditional expression of the neuropathogenic mhtt-exon1 protein, they may be useful in studying Huntington's disease (HD) or other polyQ disorders. Of note, sequencing of the polyQ region (using mice from the 11th backcross) indicate the actual number of repeats to be 98.For example, when bred to strains expressing cre in brain tissues (such as Nestin-Cre (see Stock No. 003771) or Emx1-Cre (see Stock No. 005628), bi-transgenic offspring show pathological cell-cell interactions critically contribute to cortical pathogenesis of HD.
Development
A targeting vector was designed with a loxP-flanked transcriptional STOP sequence immediately upstream of a polyQ-mutant form of the human Huntingtin protein exon 1 (mhtt-exon1) sequence (containing 103 mixed CAA-CAG repeats, each encoding glutamine), all followed by a polyadenylation sequence. This targeting construct was incorporated into the Gt(ROSA)26Sor locus via electroporation into (129X1/SvJ x 129S1/Sv)F1-derived R1 embryonic stem (ES) cells. Correctly targeted ES cells were microinjected into C57BL/6J blastocysts. The resulting "RosaHD" mutant mice were subsequently backcrossed to C57BL/6J mice for at least 11 generations prior to arrival at The Jackson Laboratory. Of note, sequencing of the polyQ region (using mice from the 11th backcross) indicate the actual number of repeats to be 98.
Control Information
| Control | ||
|---|---|---|
| Wild-type from the colony | ||
| 000664 C57BL/6J | ||
| Considerations for Choosing Controls | ||
Related Strains
Strains carrying other alleles of Gt(ROSA)26Sor
View Strains carrying other alleles of Gt(ROSA)26Sor (64 strains)
Additional Web Information
Introduction to Cre-lox technology
Phenotype
Phenotype Information
Huntington Disease; HD - Models with phenotypic similarity to human disease where etiologies are distinct.2
2 Human genes are associated with this disease. Orthologs of those genes do not appear in the mouse genotype(s).
assigned by genotype
The following phenotype relates to a compound genotype created using this strain.
Contact JAX® Services jaxservices@jax.org for customized breeding options.Gt(ROSA)26Sortm1(HD*103Q)Xwy/? Tg(Nes-cre)1Kln/?
involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * SJL (conditional)
- nervous system phenotype
- abnormal inhibitory postsynaptic currents (MGI Ref ID J:99759)
- spontaneous inhibitory postsynaptic current frequency but not amplitude is significantly decreased; however no change in spontaneous excitatory postsynaptic currents is seen
- abnormal pyramidal neuron morphology (MGI Ref ID J:99759)
- 35 of 37 neurons display dysmorphic axons compared to only 5 of 40 wild-type axons in cortex in 6-month old mice
- gliosis (MGI Ref ID J:99759)
- the density of GFAP+ cells is increased 9-fold and 6-fold in the cortex and striatum, respectively, compared to wild-type littermates at 6 months
- neurodegeneration (MGI Ref ID J:99759)
- at 1 year of age, an increase in degenerating neurons, including pyramidal neurons, is seen in the cortex compared to wild-type mice
- behavior/neurological phenotype
- hypoactivity (MGI Ref ID J:99759)
- activity is reduced at 6, 8, and 10 months of age but not at 2 months of age
This mouse can be used to support research in many areas including:
Mouse/Human Gene Homologs
Huntington's disease (chorea)
Neurobiology Research
Ataxia (Movement) Defects
Behavioral and Learning Defects
Huntington's disease
Neuromuscular Defects
Research Tools
Cre-lox System
loxP-flanked Sequences
Genes & Alleles
Gene & Allele Information
| Allele Symbol | Gt(ROSA)26Sortm1(HD*103Q)Xwy | ||
|---|---|---|---|
| Allele Name | targeted mutation 1, X William Yang | ||
| Allele Type | Targeted (knock-in) | ||
| Common Name(s) | RosaHD; mhtt-exon1 (103Q); | ||
| Strain of Origin | (129X1/SvJ x 129S1/Sv)F1-Kitl+ | ||
| ES Cell Line Name | R1 | ||
| ES Cell Line Strain | (129X1/SvJ x 129S1/Sv)F1-Kitl<+> | ||
| Gene Symbol and Name | Gt(ROSA)26Sor, gene trap ROSA 26, Philippe Soriano | ||
| Chromosome | 6 | ||
| Gene Common Name(s) | AV258896; Gtrgeo26; Gtrosa26; R26; ROSA26; beta geo; expressed sequence AV258896; gene trap ROSA 26; gene trap ROSA b-geo 26; | ||
| Molecular Note | A targeting vector was designed with a loxP-flanked transcriptional STOP sequence immediately upstream of a neuropathogenic polyQ-mutant form of the human Huntingtin protein exon 1 (mhtt-exon1) sequence (containing 103 mixed CAA-CAG repeats, each encoding glutamine), all followed by a polyadenylation sequence. When these mice are bred with animals expressing cre under the control of a promoter of interest, The STOP signal is deleted in tissue of interest allowing conditional expression of mhtt1-exon1. [MGI Ref ID J:123199] [MGI Ref ID J:99759] | ||
Genotyping
Genotyping Information
Genotyping Protocols
HD*103Q, Standard PCR
Gt(ROSA)26Sortm1(HD*103Q)Xwy, Standard PCR
Helpful Links
Genotyping resources and troubleshooting
References
References
Selected Reference(s)
Gu X; Li C; Wei W; Lo V; Gong S; Li SH; Iwasato T; Itohara S; Li XJ; Mody I; Heintz N; Yang XW. 2005. Pathological cell-cell interactions elicited by a neuropathogenic form of mutant Huntingtin contribute to cortical pathogenesis in HD mice. Neuron 46(3):433-44. [PubMed: 15882643] [MGI Ref ID J:99759]
Additional References
Gt(ROSA)26Sortm1(HD*103Q)Xwy relatedKazantsev A; Preisinger E; Dranovsky A; Goldgaber D; Housman D. 1999. Insoluble detergent-resistant aggregates form between pathological and nonpathological lengths of polyglutamine in mammalian cells. Proc Natl Acad Sci U S A 96(20):11404-9. [PubMed: 10500189] [MGI Ref ID J:123199]
Health & husbandry
Health & Colony Maintenance Information
Animal Health Reports
Room Number AX12
Colony Maintenance
Breeding & Husbandry When maintaining a live colony, heterozygous mice may be bred to wildtype siblings or to C57BL/6J inbred mice. While presumed to be viable and fertile, the phenotype of homozygous mice has not been reported (Aug-2007). Mating System Heterozygote x +/+ sibling (Female x Male) 01-JAN-08 Diet Information LabDiet® 5K52/5K67
Purchasing information
Pricing, Supply Level & Notes, Controls, General Terms & Conditions
Pricing
| Pricing for USA, Canada and Mexico shipping destinations |
|
Weeks of Age Price (US dollars $) Gender Genotypes Provided Individual Mouse $243.50 Female or Male Heterozygous for Gt(ROSA)26Sortm1(HD*103Q)Xwy
Pairs /Price (US dollars $) Pair Genotype $297.85 Heterozygous for Gt(ROSA)26Sortm1(HD*103Q)Xwy x Wild-type for Gt(ROSA)26Sortm1(HD*103Q)Xwy $297.85 Wild-type for Gt(ROSA)26Sortm1(HD*103Q)Xwy x Heterozygous for Gt(ROSA)26Sortm1(HD*103Q)Xwy
Additional Supply Details
| Pricing for International shipping destinations |
|
Weeks of Age Price (US dollars $) Gender Genotypes Provided Individual Mouse $316.60 Female or Male Heterozygous for Gt(ROSA)26Sortm1(HD*103Q)Xwy
Pairs /Price (US dollars $) Pair Genotype $387.30 Heterozygous for Gt(ROSA)26Sortm1(HD*103Q)Xwy x Wild-type for Gt(ROSA)26Sortm1(HD*103Q)Xwy $387.30 Wild-type for Gt(ROSA)26Sortm1(HD*103Q)Xwy x Heterozygous for Gt(ROSA)26Sortm1(HD*103Q)Xwy
Additional Supply Details
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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 approximately 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 two business days following order placement. |
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| Supply Notes |
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Control Information
| Control | ||
|---|---|---|
| Wild-type from the colony | ||
| 000664 C57BL/6J | ||
| 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. | ||
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