Mice that are homozygous null for the Bcr gene are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. No Bcr gene product (mRNA or protein) is detected. Homozygous null animals are more susceptible to lipopolysaccharide (LPS) -induced endotoxemia. Sublethal doses of LPS induce septic shock characterized by a pronounced, sustained neutrophilia and tissue damage to multiple organs. Tissue damage is mediated by neutrophils that exhibit an elevated superoxide production resulting in similarly elevated respiratory burst. Neutrophils obtained from null animals that have been activated in vitro with phorbol myristate actetate (PMA) show an almost 100% increase in respiratory burst over that seen in wildtype neutrophils.
A targeting vector containing a neomycin resistance gene driven by the mouse phosphoglycerate kinase promoter was used to disrupt a portion of intron 1 and exon2 of the Bcr gene. The construct was electroporated into 129S2/SvPas-derived D3 embryonic stem (ES) cells. A herpes simplex virus thymidine kinase was used for negative selection. Correctly targeted ES cells were injected into C57BL/6J blastocysts. The resulting chimeric male animals were backcrossed to C57BL/6J females.
|Allele Name||targeted mutation 1, Nora Heisterkamp|
|Allele Type||Targeted (Null/Knockout)|
|Gene Symbol and Name||Bcr, breakpoint cluster region|
|Strain of Origin||129S2/SvPas|
|Molecular Note||Exon 2 was partially replaced by insertion of a neomycin resistance expression cassette. Northern blot analysis with an exon 1 specific probe demonstrated that the transcript was not expressed in brain of homozygous mice, and western blot analysis on brain extracts showed that no protein was produced in homozygotes.|
|Mutations Made By|| |
Nora Heisterkamp, Childrens Hospital Los Angeles
This strain originated on a B6;129S2 background. It was crossed with a Black Swiss mouse for an unknown number of generations before being made homozygous. The donating investigator recommends that males not be housed together.
When using the bcr- mouse strain in a publication, please cite the originating article(s) and include JAX stock #003803 in your Materials and Methods section.