Mice heterozygous for a null Atp2a2 or SERCA2 allele exhibit a reduction in cardiac contractility, reduced blood pressure and squamous cell tumors of keratinized epithelial tissues (90% in aged mice). Homozygous embryos do not survive. This strain may be useful for studying heart disease and Darier-White disease (keratosis follicularis).
Gary E Shull, University of Cincinnati
Genetic Background | Generation |
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Allele Type | Gene Symbol | Gene Name |
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Targeted (Null/Knockout) | Atp2a2 | ATPase, Ca++ transporting, cardiac muscle, slow twitch 2 |
Atp2a2 or SERCA2 (Ca++ transporting ATPase, cardiac muscle, slow twitch 2) encodes an intracellular pump located in the sarcoplasmic or endoplasmic reticula of muscle cells. This ATPase is involved in the cardiac contraction/relaxation cycle and in calcium translocation. Mutations in ATP2A2 are associated with Darier-White disease (keratosis follicularis). Mice heterozygous for this allele are viable and fertile. Homozygous embryos do not survive. Heterozygotes exhibit a reduction in cardiac contractility, reduced blood preesure, susceptibility to cardiac disease in response to
pressure overload, and a reduced force-frequency response in heart. Approximately 90% of aging (50+ weeks) heterozygotes develop squamous cell tumors of keratinized epithelial tissues (including stomach, esophagus, tongue, oral mucosa, and skin). This strain may be useful for studying heart disease and Darier-White disease.
A targeting vector containing the neomycin resistance and herpes simplex virus thymidine kinase genes was used to disrupt part of the promoter, the transcription initiation site and exons 1, 2 and part of 3. The construct was electroporated into 129X1/SvJ-derived embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts. The resulting chimeric animals were crossed to Black Swiss mice. Mice from the colony were backcrossed to FVB/N for at least 10 generations. Upon arrival, mice were bred to FVB/NJ for at least 1 generation to establish the colony.
Allele Name | targeted mutation 1, Gary E Shull |
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Allele Type | Targeted (Null/Knockout) |
Allele Synonym(s) | SERCA2a knockout; SERCA2a- |
Gene Symbol and Name | Atp2a2, ATPase, Ca++ transporting, cardiac muscle, slow twitch 2 |
Gene Synonym(s) | |
Strain of Origin | 129X1/SvJ |
Chromosome | 5 |
Molecular Note | A genomic fragment containing the promoter, transcription initiation site, the first two exons and part of the third exon was replaced with a neomycin selection cassette. |
While maintaining a live colony, these mice are bred as heterozygotes. Mice homozygous for the mutation are not viable.
When using the FVB.129X1(Cg)-Atp2a2tm1Ges/Mmjax mouse strain in a publication, please cite the originating article(s) and include MMRRC stock #36806 in your Materials and Methods section.
Facility Barrier Level Descriptions
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.
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