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Crosses of p53LSL-wt/+, p53LSL-53,54/+ or p53LSL-25,26,53,54/+ with p53+/+; CMV-Cre mice yield the expected numbers of p53wt/+ and p5353,54/+ pups but not p5325,26,53,54/+ pups at postnatal day 21 (P21). X denotes wild-type or mutant allele. The observed numbers of live and dead pups compared with the expected numbers of live pups are indicated: [Observed (Expected)]. p5353,54 mutations in the second TAD did not perturb the transcriptional activity of p53 at the genome-wide level and provide a control for the mutation of only these residues. The presence of viable p53wt/+ and p5353,54/+ pups suggests that re-expression of p53 in early development using this system does not cause developmental defects. The binomial distribution statistical test shows that the absence of p5325,26,53,54/+ pups at P21 is significant. *, P = 7.65 × 10−18.