B6.129X1-Bid^tm1Sjk/J

Stock number: 008887
Research areas: Apoptosis Research, Research Tools

Description

Mice that are homozygous for this Bid (BH3 interacting domain death agonist) targeted mutation resistant to hypoxia-ischemia (HI) injury, experimentally induced apoptosis, and oxygen toxicity under hyperoxic conditions. This mutant mouse strain may be useful in studies of mitochondiral activation in apoptosis, and ischemic cell injury and death.

Detailed description

Mice that are homozygous for the targeted mutation are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. No gene product (protein) is detected by Western blot analysis of spleen and thymus tissue. Most homozygotes survive injection of anti-Fas antibodies while wildtype mice succumb to acute liver failure within hours. Mutant mice are resistant to hypoxia-ischemia (HI) injury, experimentally induced apoptosis, and oxygen toxicity under hyperoxic conditions. Homozygotes exhibit reduced lysosome permeability and diminished reactive oxygen species generation. Isolated neurons are resistant to oxygen/glucose deprivation induced cell death. This mutant mouse strain may be useful in studies of mitochondiral activation in apoptosis, and ischemic cell injury and death.

Development

A targeting vector containing a PGK-neo cassette was used to disrupt exons 1 and 2 and part of exon 3. The construct was electroporated into 129X1/SvJ derived RW-4 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts. The resulting chimeric animals were crossed to C57BL/6 mice, and then backcrossed to C57BL/6 for 12 generations before arriving at The Jackson Laboratory.

Allele

Symbol: Bid^tm1Sjk
Name: targeted mutation 1, Stanley J Korsmeyer
MGI accession ID: MGI:2158671
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Bid
Marker name: BH3 interacting domain death agonist
Chromosome: 6
Strain of origin: 129X1/SvJ
Molecular note: A 4.2 kb genomic fragment containing exons 1, 2 and part of 3 was replaced with a neomycin selection cassette inserted in reverse transcriptional orientation to the gene. The deleted sequences encode the BH3 domain of the protein. Western blot analysis on spleen and thymus samples derived from homozygous mice demonstrated that no detectable protein is produced from this allele.