B6;129-Trp53^tm2Xu/J

Stock number: 006980
Product name: p53S18/23A
Research areas: Apoptosis Research, Cancer Research, Immunology, Inflammation and Autoimmunity Research

Description

Mice homozygous for this targeted mutation lack Trp53-dependent apoptosis and develop a distinct range of spontaneous malignancies.

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 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 in cancer development and apoptosis.

Development

Missense mutations resulting in serine (Ser) to alanine (Ala) amino acid substitutions at codons 18 and 23 in exon 2 were engineered using site-directed mutagenesis. A targeting vector containing the Ser18/23Ala mutations and a loxP-flanked (floxed) PGK-Neo resistance cassette inserted into intron 4 was injected into 129S6/SvEvTac-derived TC-1 embryonic stem (ES) cells. F1 mutant heterozygous mice were bred to CMV-Cre transgenic mice on a C57BL/6 X 129 mixed genetic background to excise the floxed PGK-Neo cassette. Homozyotes were created by intercrossing heterozygotes.

Allele

Symbol: Trp53^tm2Xu
Name: targeted mutation 2, Yang Xu
MGI accession ID: MGI:3629221
Generation method: Targeted
Synonyms: p53^S18/23A
Marker symbol: Trp53
Marker name: transformation related protein 53
Marker synonyms: BCC7; BMFS5; LFS1; p44; p53; TRP53
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.