B6.129S6-Trp53^tm2Xu/J

Stock number: 007218
Research areas: Apoptosis Research, Cancer Research, Immunology, Inflammation and Autoimmunity Research

Description

This targeted mutation of Trp53 (transformation related protein 53) contains two phosphorylation site disruptions: Ser18 to Ala (S18A), and Ser23 to Ala (S23A). Trp53-dependent apoptosis is essentially abolished in thymocytes from mice homozygous for this allele. This mutant mouse strain may be useful in studies of phosphorylation events, cancer development and apoptosis.

Detailed description

Mice homozygous for this targeted mutation are viable and fertile. They carry two phosphorylation site disruptions: Ser18 to Ala (S18A), and Ser23 to Ala (S23A). Trp53-dependent apoptosis is essentially abolished in thymocytes. These mice develop spontaneous tumors at approximately 1.5 years of age and also develop a range of malignancies that are distinct from those found in animals carrying either a single S23A mutation or a complete knockout of the gene. This mutant mouse strain may be useful in studies of phosphorylation events, cancer development and apoptosis.

In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. It should be noted that the phenotype could vary from that originally described. We will modify the strain description if necessary as published results become available.

Development

A targeting vector containing Ser18 to Ala, and Ser23 to Ala mutations, in addition to a "floxed" PGK-Neo resistance cassette in exon 4, was injected into 129S6/SvEvTac-derived TC-1 embryonic stem (ES) cells. F1 mutant heterozygous mice were bred to CMV-Cre transgenic mice to excise the "floxed" PGK-Neo cassette. Homozyotes were created by intercrossing heterozygous mice prior to arrival at The Jackson Laboratory (as Stock No. 006980). Upon arrival, some mice were backcrossed to C57BL/6J for at least five generations to generate this congenic strain (Stock No. 007218).

Allele

Symbol: Trp53^tm2Xu
Name: targeted mutation 2, Yang Xu
MGI accession ID: MGI:3629221
Generation method: Targeted
Marker symbol: Trp53
Marker name: transformation related protein 53
Chromosome: 11
Strain of origin: 129S6/SvEvTac
Molecular note: Site-directed mutagenesis within exon 2 generated missense mutations at codons 18 and 23, resulting in the substitutions of both serines with alanines (p.S18A, p.S23A). A single loxP site remained in intron 4 after a loxP site flanked neomycin resistance gene cassette was excised via Cre-mediated recombination. Sequencing verified that only the S18/23A mutations were present in mutant mice.