C57BL/6-Bbc3^tm1Ast/J

Stock number: 011067
Research areas: Apoptosis Research, Cancer Research, Cell Biology Research, Research Tools

Description

Thymocytes and mouse embryonic fibroblasts from homozygous knock-out Bbc3^tm1Ast (commonly referred to as puma^-) mice are resistant to DNA-damage induced apoptosis. This mutant mouse strain may be useful in studies of apoptosis and oxidative stress.

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 (mRNA) is detected by RT-PCR analysis of irradiated thymocytes from homozygotes and Northern blot analysis of thymus and spleen from homozygotes. MEFs and thymocytes from homozygous mice exhibit increased resistance to DNA-damage induced apoptosis after treatment by etoposide and gamma radiation. Neurons from homozygotes are more resistant to oxidative stress induced and endoplasmic reticulum (ER) stress induced apoptosis than wildtype controls.

Development

A targeting vector containing a floxed PGK-neo cassette was used to disrupt exons 2 and 3, which encode the BH3 interaction domains. The construct was electroporated into C57BL/6 derived Bruce4 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts. The resulting chimeric animals were crossed to mice expressing Cre recombinase, on the C57BL/6 background, to remove the selection cassette. Upon arrival at The Jackson Laboratory the mice were crossed once to C57BL/6J to establish the colony.

Allele

Symbol: Bbc3^tm1Ast
Name: targeted mutation 1, Andreas Strasser
MGI accession ID: MGI:2681654
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Bbc3
Marker name: BCL2 binding component 3
Chromosome: 7
Strain of origin: B6.Cg-Thy1^a
Molecular note: Exons 2 and 3 which contain the BH3 interaction domain were replaced by a floxed PGK-neomycin expression cassette. The resistance cassette was removed in vivo by crossing mice to a C57BL/6 Deleter mouse line. Gene disruption was confirmed by RT-PCR and Northern blot analysis.