A novel genetic modifier of p53, mop1, results in embryonic lethality

A novel genetic modifier of p53, mop1, results in embryonic lethality 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. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Mammalian Genome Springer Journals

A novel genetic modifier of p53, mop1, results in embryonic lethality

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Publisher
Springer Journals
Copyright
Copyright © 2004 by Springer-Verlag
Subject
Philosophy
ISSN
0938-8990
eISSN
1432-1777
D.O.I.
10.1007/s00335-004-2327-y
Publisher site
See Article on Publisher Site

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.

Journal

Mammalian GenomeSpringer Journals

Published: Jan 1, 2004

References

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