Genetic mapping of Mom5, a novel modifier of Apc(Min)-induced intestinal tumorigenesis

Seija I Oikarinen1, Alicia G Cleveland, Karlene M Cork

  • 1Department of Applied Chemistry and Microbiology (Nutrition), University of Helsinki, PO Box 66, Helsinki FIN-00014, Finland.

Carcinogenesis
|July 4, 2009
PubMed

Insights

Estrogen receptor beta (ERbeta) plays a role in intestinal cancer. A genetic modifier, Mom5, on chromosome 5, significantly reduces intestinal tumor number in mice.

Area of Science:

  • Genetics
  • Cancer Biology
  • Endocrinology

Background:

  • Estrogen receptor beta (ERbeta) is implicated in various biological processes.
  • Intestinal tumorigenesis is a complex process influenced by multiple genetic factors.
  • Apc(Min) mice are a standard model for studying intestinal polyposis.

Purpose of the Study:

  • To investigate the role of ERbeta in intestinal tumorigenesis using ERbeta knockout (ERbeta(-/-)) Apc(Min) mice.
  • To identify genetic modifiers influencing tumor development in Apc(Min) mice on a mixed genetic background.

Main Methods:

  • Backcrossing ERbeta knockout mice to a B6 genetic background for 10 generations.
  • Performing a test cross at the N(5) generation with Apc(Min/+) mice.
  • Evaluating intestinal tumorigenesis and conducting genetic linkage analysis.

Main Results:

  • A significant genetic modifier of tumor number, Modifier of Min 5 (Mom5), was localized to mouse chromosome 5.
  • The 129P2 allele of Mom5 was associated with a 50% reduction in mean intestinal tumor number.
  • Rad50-interacting protein-1 was identified as a strong candidate gene for Mom5.

Conclusions:

  • ERbeta's role in intestinal tumorigenesis requires further investigation on a uniform genetic background.
  • Mom5 represents a novel genetic locus that significantly impacts intestinal tumor burden in Apc(Min) mice.
  • The identification of Rad50-interacting protein-1 provides a new avenue for understanding intestinal cancer development.

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