Mouse embryonic fibroblasts from knock-out homozygotes exhibit a slight survival advantage when treated with apoptosis inducers. These mutant mice may be useful in studies of mitochondrial events of apoptosis, especially when paired with other executioner caspase mutant models.
Dr. Richard A. Flavell, Yale University School of Medicine
Homozygous mice are viable and fertile with normal appearance, organ morphology, and lymphoid development. Endogenous protein expression is absent in all tissues tested (including brain, thymus, heart, lung, liver, spleen, kidney, and skeletal muscle). Mouse embryonic fibroblasts (MEFs) from homozygotes exhibit a slight survival advantage when treated with apoptosis inducers, but other cell subsets undergo normal apoptosis (including activated T cells death following T cell receptor stimulation, thymocyte apoptosis, and Fas-mediated B cell and hepatocyte cell death). These mutant mice may be useful in studies of mitochondrial events of apoptosis, especially when paired with other executioner caspase mutant models.
A targeting vector was designed to replace exons 2 and 3 of the endogenous gene with a neomycin resistance cassette and to introduce a frame-shift mutation in the remaining downstream sequence. The construct was electroporated into 129S6/SvEvTac-derived TC1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts and the resulting chimeric males were bred to C57BL/6 females. The donating investigator reports that heterozygous mice were backcrossed to C57BL/6 mice for 10 generations before arrival at The Jackson Laboratory (see SNP note below).
A 32 SNP (single nucleotide polymorphism) panel analysis, with 27 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the rederived living colony at The Jackson Laboratory Repository. While the 27 markers throughout the genome suggested a C57BL/6 genetic background, 4 of 5 markers that determine C57BL/6J from C57BL/6N were found to be segregating. One of these markers that was not segregating is found on Chromosome 19, where Casp7 resides. These data suggest the mice sent to The Jackson Laboratory Repository were on a C57BL/6N genetic background.
|Allele Name||targeted mutation 1, Richard A Flavell|
|Allele Type||Targeted (Null/Knockout)|
|Gene Symbol and Name||Casp7, caspase 7|
|Strain of Origin||129S6/SvEvTac|
|Molecular Note||The targeting construct replaces exons 2 and 3 with a neomycin resistance cassette, and also results in a frame-shift. Western blot analysis showed absence of caspase 7 expression in homozygous mice.|
|Mutations Made By|| |
Dr. Richard Flavell, Yale University School of Medicine
When maintaining a live colony, these mice are bred as homozygotes.
When using the Casp7- mouse strain in a publication, please cite the originating article(s) and include JAX stock #006237 in your Materials and Methods section.