Journal Article

Genetic mapping of <i>Mom5</i>, a novel modifier of <i>Apc<sup>Min</sup></i>-induced intestinal tumorigenesis

Seija I. Oikarinen, Alicia G. Cleveland, Karlene M. Cork, Kimberly K. Bynoté, Joseph J. Rafter, Jan-Åke Gustafsson, Marja Mutanen and Karen A. Gould

in Carcinogenesis

Volume 30, issue 9, pages 1591-1596
Published in print September 2009 | ISSN: 0143-3334
Published online July 2009 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgp159
Genetic mapping of Mom5, a novel modifier of ApcMin-induced intestinal tumorigenesis

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The initial purpose of this study was to assess the role of estrogen receptor β (ERβ) in intestinal tumorigenesis by examining the effects of an ERβ knockout (ERβ−/−) on ApcMin mice. In order to accomplish this goal on a uniform genetic background, we were required to backcross the ERβ knockout from the 129P2 genetic background to the B6 genetic background for 10 generations. Midway through this process, we performed a test cross in which mice from the N5 backcross generation of the ERβ knockout strain were intercrossed with ApcMin/+ mice to obtain ApcMin/+ ERβ+/+, ApcMin/+ ERβ+/− and ApcMin/+ ERβ−/− mice. Intestinal tumorigenesis in the N5F2 mice was evaluated at 14 weeks of age. The analysis of the impact of ERβ in the N5 cross was complicated by segregating 129P2-derived alleles that affected tumor number and were unlinked to ERβ. Genetic linkage analysis of this cross permitted the localization of a single genetic modifier of tumor number in ApcMin/+ mice. This locus, Modifier of Min 5 (Mom5), maps to proximal mouse chromosome 5; the 129P2 allele of this locus is associated with a 50% reduction in mean intestinal tumor number. Through in silico analysis and confirmatory sequencing, we have identified the Rad50-interacting protein-1 gene as a strong candidate for Mom5.

Journal Article.  4812 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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