FVB.129X1(Cg)-Atp2a2^tm1Ges/Mmjax

Stock number: 022036
Research areas: Cancer Research, Cardiovascular Research, Cell Biology Research, Developmental Biology Research

Description

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).

Detailed description

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.

Development

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

Symbol: Atp2a2^tm1Ges
Name: targeted mutation 1, Gary E Shull
MGI accession ID: MGI:2158235
Generation method: Targeted
Attributes: Null/Knockout
Synonyms: SERCA2a knockout; SERCA2a^-
Marker symbol: Atp2a2
Marker name: ATPase, Ca++ transporting, cardiac muscle, slow twitch 2
Chromosome: 5
Strain of origin: 129X1/SvJ
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.