title: Genetic mapping of Mom5, a novel modifier of Apc(Min)-induced intestinal tumorigenesis.
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.
authors: Department of Applied Chemistry and Microbiology (Nutrition), University of Helsinki, PO Box 66, Helsinki FIN-00014, Finland.
authors: Seija I
authors: SI
authors: Oikarinen
authors: Alicia G
authors: AG
authors: Cleveland
authors: Karlene M
authors: KM
authors: Cork
authors: Kimberly K
authors: KK
authors: Bynoté
authors: Joseph J
authors: JJ
authors: Rafter
authors: Jan-Ake
authors: JA
authors: Gustafsson
authors: Marja
authors: M
authors: Mutanen
authors: Karen A
authors: KA
authors: Gould
mesh_terms: D000236:Adenoma / Q000235:genetics; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics; D002874:Chromosome Mapping; D003433:Crosses, Genetic; D047629:Estrogen Receptor beta / Q000235:genetics / Q000502:physiology*; D005095:Exoribonucleases; D005260:Female; D017491:Genes, APC; D007414:Intestinal Neoplasms / Q000209:etiology / Q000235:genetics*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data
chemical_list: D002352:Carrier Proteins; D047629:Estrogen Receptor beta; D005095:Exoribonucleases; C443126:Prnpip1protein, mouse