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Mammalian Genome

, Volume 15, Issue 6, pp 415–423 | Cite as

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

  • Susan C. Evans
  • Min Liang
  • Christopher Amos
  • Xiangjun Gu
  • Guillermina Lozano
Original Contributions

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.

Keywords

Genetic Modifier Embryonic Lethality Congenic Mouse Simple Sequence Length Polymorphism Recessive Locus 

Notes

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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Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  • Susan C. Evans
    • 1
  • Min Liang
    • 1
  • Christopher Amos
    • 2
  • Xiangjun Gu
    • 2
  • Guillermina Lozano
    • 3
  1. 1.Department of Chemistry and BiochemistryOhio UniversityAthensUSA
  2. 2.Department of EpidemiologyThe University of Texas M.D. Anderson Cancer CenterHoustonUSA
  3. 3.Department of Molecular GeneticsThe University of Texas M.D. Anderson Cancer CenterHoustonUSA

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