Mice homozygous for this targeted mutation lack Trp53-dependent apoptosis and develop a distinct range of spontaneous malignancies.
Yang Xu, University of California, San Diego
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.
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 Name||targeted mutation 2, Yang Xu|
|Gene Symbol and Name||Trp53, transformation related protein 53|
|Promoter||Trp53, transformation related protein 53, mouse, laboratory|
|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. A single loxP site remained in intron 4 after a floxed PGK-neo cassette was excised via cre-mediated recombination. Sequencing verified that only the S18/23A mutations were present in mutant mice.|
|Mutations Made By|| |
Yang Xu, University of California, San Diego
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