B6;129-Trp53bp1^tm1Jc/J

Stock number: 006495
Research areas: Cancer Research, Cell Biology Research, Developmental Biology Research, Immunology, Inflammation and Autoimmunity Research, Internal/Organ Research, Research Tools

Description

These mutant mice may be useful in studies of the immune system, cancer, tumor suppression, and DNA damage response pathways.

Detailed description

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.

Development

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

Symbol: Trp53bp1^tm1Jc
Name: targeted mutation 1, Junjie Chen
MGI accession ID: MGI:2654201
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Trp53bp1
Marker name: transformation related protein 53 binding protein 1
Chromosome: 2
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.