B6N.129S1-Casp3^tm1Flv/J

Stock number: 006233
Product name: CPP32-
Research areas: Apoptosis Research, Cardiovascular Research, Developmental Biology Research, Immunology, Inflammation and Autoimmunity Research, Mouse/Human Gene Homologs, Reproductive Biology Research, Research Tools, Sensorineural Research

Description

Brain development in Casp3-deficient mice shows a variety of hyperplasias and disorganized cell deployment, and ovaries from female homozygotes show aberrant development. These mutant mice may be useful in studies of apoptosis, ovarian follicle and corpus luteum development, and eye and ear development

Detailed description

On this C57BL/6 congenic background, homozygotes are viable, fertile, and reach adulthood, but females reported display suboptimal mothering instincts. Functional endogenous protein and mRNA are absent from all tissues tested. Homozygous mice are resistant to in vivo cerebral ischemia/reperfusion and in vitro oxygen-glucose deprivation. Ovaries from female homozygotes show aberrant atretic follicles associated with a granulosa cell-intrinsic defect in apoptosis as well as defective corpus luteum regression. Homozygous mice are congenitally deaf with hair cell defects in the Organ of Corti. Optic lens formation/morphology also is abnormal with cataracts at the anterior lens pole. Of note, these mice lack the embryonic/perinatal-lethal brain pathology observed in mutant mice on the 129 and mixed B6;129 genetic backgrounds. These mutant mice may be useful in studies of apoptosis, ovarian follicle and corpus luteum development, and eye and ear development.

Development

A targeting vector was designed to replace the caspase protease-conserved catalytic site of the endogenous gene with a PGK-neo cassette. The construct was electroporated into 129S1/Sv-derived W9.5 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts, and the resulting chimeric males were bred to C57BL/6 females. Heterozygous mice were backcrossed to C57BL/6 mice for ten generations (see SNP results below) prior to sending females and males to The Jackson Laboratory Repository in 2006. Upon arrival, these females and males were used to establish our living mouse 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. While the 27 markers throughout the genome suggested a C57BL/6 genetic background, all 5 markers that determine C57BL/6J from C57BL/6N were found to be C57BL/6N allele-type. These data suggest the mice sent to The Jackson Laboratory Repository were on a C57BL/6N genetic background, the living colony is on a C57BL/6N genetic background, and the sperm frozen in 2008 is on a C57BL/6N genetic background.

Allele

Symbol: Casp3^tm1Flv
Name: targeted mutation 1, Richard Flavell
MGI accession ID: MGI:2158753
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Casp3
Marker name: caspase 3
Chromosome: 8
Strain of origin: 129S1/Sv-Oca2⁺ Tyr⁺ Kitl⁺
Molecular note: A genomic fragment containing sequences encoding a conserved motif was replaced with a neomycin selection cassette. RT-PCR analysis on samples derived from brain and liver of homozygous mice demonstrated that no detectable transcript is produced from this allele. Western blot analysis on samples derived from thymocytes of homozygous mice confirmed that no detectable protein was produced.