B6;129S4-Trp53^tm4Tyj/J

Stock number: 008181
Research areas: Cancer Research

Description

Mice homozygous for this S23A point mutation are viable and fertile. Cells from the mice, including thymocytes and neurons in the cerebellum, exhibit defective apoptosis in response to DNA damage and exhibit partially impaired TRP53 (p53) stabilization. Mice develop increased lymphomas (especially B-cell lineage) and other tumors between one and two years of age.

Detailed description

Mice homozygous for this S23A point mutation are viable and fertile. Cells from the mice, including thymocytes and neurons in the cerebellum, exhibit defective apoptosis in response to DNA damage and exhibit partially impaired TRP53 (p53) stabilization. Mice develop increased lymphomas (especially B-cell lineage) and other tumors between one and two years of age.

Development

A targeting vector was designed to introduce a Ser23Ala point mutation to exon 2 of the gene and place a loxP-flanked puromycin resistance cassette in reverse orientation in intron 1. The construct was electroporated into 129S4/SvJae-derived J1 embryonic stem (ES) cells. Cre recombinase was introduced to targeted ES cells by transient transfection to delete the puromycin cassette. The strain has been maintained on a mixed 129S4/SvJae and C57BL/6 by the donating laboratory.

Allele

Symbol: Trp53^tm4Tyj
Name: targeted mutation 4, Tyler Jacks
MGI accession ID: MGI:3056071
Generation method: Targeted
Attributes: Not Specified
Synonyms: S23A
Marker symbol: Trp53
Marker name: transformation related protein 53
Marker synonyms: BCC7; BMFS5; LFS1; p44; p53; TRP53
Chromosome: 11
Strain of origin: 129S4/SvJae
Molecular note: Serine codon 23 (TCA) in exon 2 was changed to alanine (GCA) (p.S23A). Transient cre recombinase expression excised a loxP site flanked puromycin resistance gene cassette that was inserted into intron1. RT-PCR of mutant MEFs confirmed correct targeting. The mutation prevents the phosphorylation of the residue in the encoded peptide.