Aging mice heterozygous for a null Atp2c1 or SPCA1 (Ca++ sequestering ATPase) allele develop an increased incidence (25%) of squamous cell tumors of keratinized epithelial cells of the skin and esophagus. Homozygous embryos do not survive beyond E10.5 as a result of Golgi stress. This strain may be useful for studying Golgi stress and its role in cancer.
Gary E Shull, University of Cincinnati
Atp2c1 or SPCA1 (Ca++ sequestering ATPase) encodes a secretory pathway Ca<2+>-ATPase located in the Golgi. This ATPase mediates Golgi uptake and regulation of cytosolic calcium and magnesium ions. Homozygous embryos do not survive beyond E10.5 as a result of Golgi stress. On a Black Swiss background, embryos exhibit incomplete neural tube closure, diminished Golgi lamellae, dilation of Golgi membranes, increased numbers of Golgi bodies, decreased numbers of ribosomes in the rough ER, increased apoptosis, and an increase in cytoplasmic lipids.
Mice heterozygous for this allele on a mixed 129 and Black Swiss background are viable and fertile, however aged (20+ months) mice have an increased incidence (25%) of squamous cell tumors of keratinized epithelial cells of the skin and esophagus.
This strain may be useful for studying Golgi stress and its role in cancer.
In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. It should be noted that the phenotype could vary from that originally described. We will modify the strain description if necessary as published results become available.
A targeting vector containing the neomycin resistance gene was used to replace exons 10-13, representing a region which includes the catalytic phosphorylation site and transmembrane domains 3 and 4. The construct was electroporated into 129-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 then backcrossed to C57BL/6 for at least 6 generations. Upon arrival, mice were bred to C57BL/6J for at least 1 generation to establish the colony.
|Allele Name||targeted mutation 1, Gary E Shull|
|Allele Type||Targeted (Null/Knockout)|
|Gene Symbol and Name||Atp2c1, ATPase, Ca++-sequestering|
|Strain of Origin||129X1/SvJ|
|Molecular Note||A neomycin selection cassette replaced exons 10-13, which encode both the catalytic phosphorylation domain and transmembrane domains 3 and 4. RT-PCR and sequencing analysis revealed expression of a mutant mRNA in which exon 9 is spliced to exon 14. Western analysis revealed decreased protein expression in heterozygous mice|
While maintaining a live colony, these mice are bred as heterozygotes. Mice homozygous for the mutation are not viable.
When using the B6.129X1(Cg)-Atp2c1tm1Ges/Mmjax mouse strain in a publication, please cite the originating article(s) and include MMRRC stock #36808 in your Materials and Methods section.