Abstract
The heterogeneity that occurs in the tumor spectrum and latency in Li-Fraumeni syndrome (LFS) patients with inherited mutations in p53 suggest risk modifiers at loci other than the major gene. We developed a mouse model to investigate these risk modifiers. Inbred CE/J mice, which succumb to multiple types of tumors similar to those found in LFS, were crossed with the p53-null 129/Sv (129-Trp53tm1Tyj) mouse. In this cross, we uncovered evidence for a genetic modifier of p53, mop1, based on an unexpected mix of genotypes in the F2 progeny from Mendelian expectations. A model in which a recessive CE/J allele in combination with p53 heterozygosity or homozygosity results in lethality most closely fits the data. Using simple-sequence length polymorphism analysis of the entire genome, we identified a putative chromosomal region for this modifier of p53 on mouse chromosome 11 centromeric to p53.
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Acknowledgments
We thank Louise Strong for her scientific discussions and Carolyn Foster and Meera Narayana for their technical help. This work was supported by NIH grant CA79743, HG02275, and CA34936.
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Evans, S., Liang, M., Amos, C. et al. A novel genetic modifier of p53, mop1, results in embryonic lethality. Mamm Genome 15, 415–423 (2004). https://doi.org/10.1007/s00335-004-2327-y
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DOI: https://doi.org/10.1007/s00335-004-2327-y