These mutant mice may be useful in studies of the immune system, cancer, tumor suppression, and DNA damage response pathways.
Junjie Chen, UTexas; M. D. Anderson Cancer Center
Homozygous "53BP1"-deficient mice are viable and fertile, but exhibit retarded growth and generate reduced litter sizes. Protein from the targeted gene is not detected in the testes (by immunoblot) or in mouse embryonic fibroblasts (MEFs) (by immunofluorescence). Homozygotes are immunocompromised, hypersensitive to whole-body irradiation, and develop thymic lymphomas with higher frequency (8%) compared to wildtype by 4-7 months of age. MEFs from homozygous mutant mice have a defective DNA damage response with impaired Chk2 activation. These mutant mice may be useful in studies of the immune system, cancer, tumor suppression, and DNA damage response pathways.
A targeting vector containing a neomycin resistance gene was used to replace the exon spanning nucleotides 3777 to 4048 of the endogenous gene. The construct was electroporated into "129/SvE"-derived embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts and chimeric males were mated to C57BL/6 females. The resulting heterozygous mice were interbred for many generations prior to arrival at The Jackson Laboratory.
|Allele Name||targeted mutation 1, Junjie Chen|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||53BP1-; Trp53bp1delta|
|Gene Symbol and Name||Trp53bp1, transformation related protein 53 binding protein 1|
|Strain of Origin||129|
|Molecular Note||The gene was disrupted by replacement of an exon containing nucleotides 3777 - 4048 with a neomycin resistance cassette via homologous recombination. Absence of gene expression in homozygous mutant animals was confirmed by Western blot analysis using an antibody directed against the N-terminal portion of the protein.|
|Mutations Made By|| |
Kay Minn, Mayo Clinic College of Medicine
When maintaining a live colony, homozygous mice are bred together. Homozygotes have an increased frequency (approximately 8%) of thymic tumors between 4-7 months of age.
When using the B6;129-Trp53bp1tm1Jc/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #006495 in your Materials and Methods section.
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