Genetic mapping of Mom5, a novel modifier of ApcMin-induced intestinal tumorigenesis

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

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Abstract

The initial purpose of this study was to assess the role of estrogen receptor β (ER β) 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/+ ER β-/-, ApcMin/+ ER β+/- and ApcMin/+ ER β-/+ mice. Intestinal tumorigenesis in the N5F2 mice was evaluated at 14 weeks of age. The analysis of the impact of ER β in the N5 cross was complicated by segregating 129P2-derived alleles that affected tumor number and were unlinked to ER β. 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.

Original languageEnglish (US)
Pages (from-to)1591-1596
Number of pages6
JournalCarcinogenesis
Volume30
Issue number9
DOIs
StatePublished - Sep 18 2009

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Estrogen Receptors
Carcinogenesis
Alleles
Neoplasms
Chromosomes, Human, Pair 5
Genetic Linkage
Computer Simulation

ASJC Scopus subject areas

  • Cancer Research

Cite this

Oikarinen, S. I., Cleveland, A. G., Cork, K. M., Bynoté, K. K., Rafter, J. J., Gustafsson, J. Å., ... Gould, K. A. (2009). Genetic mapping of Mom5, a novel modifier of ApcMin-induced intestinal tumorigenesis. Carcinogenesis, 30(9), 1591-1596. https://doi.org/10.1093/carcin/bgp159

Genetic mapping of Mom5, a novel modifier of ApcMin-induced intestinal tumorigenesis. / Oikarinen, Seija I.; Cleveland, Alicia G.; Cork, Karlene M.; Bynoté, Kimberly K.; Rafter, Joseph J.; Gustafsson, Jan Åke; Mutanen, Marja; Gould, Karen A.

In: Carcinogenesis, Vol. 30, No. 9, 18.09.2009, p. 1591-1596.

Research output: Contribution to journalArticle

Oikarinen, SI, Cleveland, AG, Cork, KM, Bynoté, KK, Rafter, JJ, Gustafsson, JÅ, Mutanen, M & Gould, KA 2009, 'Genetic mapping of Mom5, a novel modifier of ApcMin-induced intestinal tumorigenesis', Carcinogenesis, vol. 30, no. 9, pp. 1591-1596. https://doi.org/10.1093/carcin/bgp159
Oikarinen SI, Cleveland AG, Cork KM, Bynoté KK, Rafter JJ, Gustafsson JÅ et al. Genetic mapping of Mom5, a novel modifier of ApcMin-induced intestinal tumorigenesis. Carcinogenesis. 2009 Sep 18;30(9):1591-1596. https://doi.org/10.1093/carcin/bgp159
Oikarinen, Seija I. ; Cleveland, Alicia G. ; Cork, Karlene M. ; Bynoté, Kimberly K. ; Rafter, Joseph J. ; Gustafsson, Jan Åke ; Mutanen, Marja ; Gould, Karen A. / Genetic mapping of Mom5, a novel modifier of ApcMin-induced intestinal tumorigenesis. In: Carcinogenesis. 2009 ; Vol. 30, No. 9. pp. 1591-1596.
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