The Trp53, transformation related protein 53, gene encodes a tumor suppressor protein, which functions as a transcription factor regulating expression of more than 100 target genes. Mutations resulting in inactivation of p53 protein facilitates tumor progression. These p53LSL-53,54 mice carry F53Q;F54S point mutations in exon 4, in the 2nd transcriptional activation domain, and a floxed STOP cassette upstream of exon 2. Expression of the mutant TRP53 protein is silenced until Cre recombinase mediates excision of the floxed STOP cassette. After Cre recombinase mediated removal of the floxed STOP cassette cells from the resulting mice exhibit no compromise in transactivation of p53 targets relative to wildtype p53. When bred to Cre recombinase expressing mice, these mice could be used to generate tumor cells for engraftment experiments. Mice that are homozygous for the targeted mutation are viable, but have decreased fertility.

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In these p53LSL-53,54 mice, which carry a mutation in the 2nd transcriptional activation domain, expression of the mutant TRP53 protein is silenced until Cre recombinase mediates excision of the floxed STOP cassette. These mice may be useful in studies of p53 function and the role of p53 as a transcriptional activator in tumor suppression.

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