These mice carry a knock-in mutation of the Atxn1 (formerly Sca1) and exhibit growth retardation, lack of motor coordination, cognitive defects, and muscle wasting, ataxia and an abnormal gait. They nay be useful in studies of neurodegenerative diseases.
Huda Zoghbi, Baylor College of Medicine
Genetic Background | Generation |
---|---|
|
Allele Type | Gene Symbol | Gene Name |
---|---|---|
Targeted (Inserted expressed sequence) | Atxn1 | ataxin 1 |
Mice that are heterozygous for the targeted mutation are viable but have a reduced lifespan (34-40 weeks). The allele consists of a 154 CAG trinucleotide repeat unit placed within exon 8 of the targeted endogenous mouse locus. Modified transcripts and protein can be detected in brain tissue. By 8 weeks of age, mutant mice exhibit noticeable growth retardation. Progressive neurological degeneration initiates by 9 weeks of age, when mutant mice begin to exhibit a clasping phenotype when held by the tail. By 20 weeks of age muscle wasting, ataxia and an abnormal gait are observed. A lack of motor coordination is detected via an accelerating rotarod test by 5 to 7 weeks. Cognitive defects include poor spatial learning performance and reduced Pavlovian conditioned fear response (impaired memory). Hippocampal basal synaptic function is impaired. Immunohistochemical and immunofluorescent analysis of brain tissue reveals neuronal intranuclear inclusions by 6 weeks of age. Older animals exhibit decreased brain weight, reduced dendritic arborization and loss of Purkinje cells. The onset and progression of the phenotype observed in these mutant mice mimics many of the features of spinaocerebellar ataxia type 1 (SCA1) and my be useful in SCA1- and neurodegenerative disease- related studies.
A targeting vector containing sequence of an expanded repeat of 154 CAGs and a floxed (loxP site flanked) neomycin resistance selection cassette was used to disrupt exon 8. The construct was electroporated into 129S7/SvEvBrd-Hprtb-m2 derived AB2.2 embryonic stem (ES) cells which were transiently transfected with a Cre recombinase vector to remove the selection cassette. Correctly targeted ES cells were injected into C57BL/6J blastocysts. The resulting chimeric animals were crossed to C57BL/6J mice, and then backcrossed to the same for 10 generations.
Allele Name | targeted mutation 1, Huda Y Zoghbi |
---|---|
Allele Type | Targeted (Inserted expressed sequence) |
Allele Synonym(s) | Atx1-KI; atxn1154Q; Sca1154Q/2Q; Sca1154Q; Sca1-KI |
Gene Symbol and Name | Atxn1, ataxin 1 |
Gene Synonym(s) | |
Promoter | Atxn1, ataxin 1, mouse, laboratory |
Strain of Origin | 129S7/SvEvBrd-Hprtb-m2 |
Chromosome | 13 |
Molecular Note | An expanded tract of 154 CAG repeats was engineered and knocked into exon 8. Additionally, a floxed neo-TK cassette was inserted into the upstream intron and subsequently deleted in ES cells via cre mediated recombination. While equivalent transcript levels were identified in both mutant and wild-type mice by RT-PCR, reduced levels of mutant protein were observed in brain tissue. The authors attributed this apparent reduction in protein level to an increased difficulty of extraction or solubilization due to the mutant protein accumulating into nuclear aggregates as mice age. |
When maintaining a live colony, these mice are bred as heterozygotes. The Donating Investigator indicates that it is best to use male carrier mice in breeding strategies because the allele appears less stable in female mutants. Additionally, the phenotype of homozygous mice is too severe for successful breeding.
When using the Sca1154Q/2Q, Atxn1[154Q] mouse strain in a publication, please cite the originating article(s) and include JAX stock #005601 in your Materials and Methods section.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
---|---|---|
Heterozygous or wild type for Atxn1<tm1Hzo>/ |
Frozen Mouse Embryo | B6.129S-Atxn1<tm1Hzo>/J Frozen Embryos | $2595.00 |
Frozen Mouse Embryo | B6.129S-Atxn1<tm1Hzo>/J Frozen Embryos | $2595.00 |
Frozen Mouse Embryo | B6.129S-Atxn1<tm1Hzo>/J Frozen Embryos | $3373.50 |
Frozen Mouse Embryo | B6.129S-Atxn1<tm1Hzo>/J Frozen Embryos | $3373.50 |
Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.
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. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.
What information were you hoping to find through your search?
How easy was it to find what you were looking for?
We may wish to follow up with you. Enter your email if you are happy for us to connect and reachout to you with more questions.
Please Enter a Valid Email Address
Thank you for sharing your feedback! We are working on improving the JAX Mice search. Come back soon for exciting changes.