These caspase 2 (Casp2) knock-out mice may be useful in studying negative and positive regulation of apoptosis, as well as oxidatively damaged cell clearance and aging.
Junying Yuan, Harvard Medical School
Mice homozygous for this caspase-2 targeted mutation are viable and fertile. As the mutation deletes the QACRG active site and the caspase-2S sequence of the endogenous enzyme, this deletion was shown to inactivate both the long and short form of caspase-2. As such, homozygous mice exhibit defects in regulation of apoptosis; including an enlarged oocyte reserve attributed to a germ cell-intrinsic death defect during prenatal ovarian development (resistance to oocyte cell death following complete cytokine starvation or exposure to an anticancer drug), as well as accelerated motor neuron cell death and defective B lymphoblast apoptosis. In addition, caspase-2-deficient mice exhibit characteristics of premature aging (including shortened maximum lifespan, impaired hair growth, increased bone loss, reduced body fat content, and higher hepatic levels of oxidized proteins). As caspase-2 acts as an upstream regulator of cell death in many cell types, caspase-2-deficient mice may be useful in studying negative and positive regulation of apoptosis, as well as oxidatively damaged cell clearance and aging.
A targeting vector was designed to replace a 1.65 kb genomic fragment (including the exon that encodes the active site pentapeptide QACRG and part of the next exon that encodes the caspase-2S sequence) of the endogenous gene with a PGKneo cassette. The construct was electroporated into 129S4/SvJae-derived J1 embryonic stem (ES) cells. The donating investigator reports that correctly targeted ES cells were injected into blastocysts and the resulting chimeric males were bred to C57BL/6J females. The donating investigator reported that mice harboring this caspase-2 mutation were backcrossed to C57BL/6J inbred mice for 7-10 generations (see SNP note below) prior to arrival at The Jackson Laboratory. Upon arrival, mice were bred with C57BL/6J inbred mice for at least one generation to establish the colony.
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. 2 of the 27 markers on Chromosomes 6 and 7 were segregating, while 1 of 5 markers that determine C57BL/6J from C57BL/6N were found to be segregating. These data suggest the mice sent to The Jackson Laboratory Repository were on a mixed C57BL/6J ; C57BL/6N genetic background.
|Allele Name||targeted mutation 1, Junying Yuan|
|Allele Type||Targeted (Null/Knockout)|
|Gene Symbol and Name||Casp2, caspase 2|
|Strain of Origin||129S4/SvJae|
|Molecular Note||A neomycin selection cassette replaced a 1.65 kb genomic fragment containing sequences that encode part of the active site of the protein and other essential regions. RT-PCR analysis on spleen mRNA derived from homozygous mice demonstrated that no detectable transcript is expressed from this allele, and western blot analysis on lysates derived from various tissues of homozygous mice confirmed that no detectable protein was encoded.|
|Mutations Made By|| |
Junying Yuan, Harvard Medical School
When maintaining a live colony, homozygous may may be bred.
When using the caspase-2- mouse strain in a publication, please cite the originating article(s) and include JAX stock #007899 in your Materials and Methods section.
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