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Updated: Jun 21, 2026

Real-time Imaging of Myeloid Cells Dynamics in ApcMin/+ Intestinal Tumors by Spinning Disk Confocal Microscopy
Published on: October 6, 2014
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.
Abstract:
The initial purpose of this study was to assess the role of estrogen receptor beta (ERbeta) in intestinal tumorigenesis by examining the effects of an ERbeta knockout (ERbeta(-/-)) on Apc(Min) mice. In order to accomplish this goal on a uniform genetic background, we were required to backcross the ERbeta 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 N(5) backcross generation of the ERbeta knockout strain were intercrossed with Apc(Min/+) mice to obtain Apc(Min/+) ERbeta(+/+), Apc(Min/+) ERbeta(+/-) and Apc(Min/+) ERbeta(-/-) mice. Intestinal tumorigenesis in the N(5)F(2) mice was evaluated at 14 weeks of age. The analysis of the impact of ERbeta in the N(5) cross was complicated by segregating 129P2-derived alleles that affected tumor number and were unlinked to ERbeta. Genetic linkage analysis of this cross permitted the localization of a single genetic modifier of tumor number in Apc(Min/+) 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.
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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