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
Genetic Background | Generation |
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Allele Type | Gene Symbol | Gene Name |
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Targeted (Null/Knockout) | Atp2c1 | ATPase, Ca++-sequestering |
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 |
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Allele Type | Targeted (Null/Knockout) |
Allele Synonym(s) | Spca1- |
Gene Symbol and Name | Atp2c1, ATPase, Ca++-sequestering |
Gene Synonym(s) | |
Strain of Origin | 129X1/SvJ |
Chromosome | 9 |
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.
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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