title: A novel genetic modifier of p53, mop1, results in embryonic lethality.
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-Trp53(tm1Tyj)) 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.
authors.affiliation: Department of Chemistry and Biochemistry, Ohio University, Athens, OH 45701, USA. evanss1@ohiou.edu
authors.forename: Susan C
authors.initials: SC
authors.lastname: Evans
authors.forename: Min
authors.initials: M
authors.lastname: Liang
authors.forename: Christopher
authors.initials: C
authors.lastname: Amos
authors.forename: Xiangjun
authors.initials: X
authors.lastname: Gu
authors.forename: Guillermina
authors.initials: G
authors.lastname: Lozano
mesh_terms: D000818:Animals; D002874:Chromosome Mapping; D005804:Genes, Lethal; D005808:Genes, Recessive; D005819:Genetic Markers; D016864:Li-Fraumeni Syndrome / Q000235:genetics*; D008126:Lod Score; D051379:Mice; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism
chemical_list: D005819:Genetic Markers; D016159:Tumor Suppressor Protein p53