title: Exclusion of Madh2, Madh4, and Madh7 as candidates for the modifier of Min 2 (Mom2) locus.
abstract: We recently identified the Modifier of Min 2 (Mom2) locus. Mom2 is a new modifier of intestinal tumorigenesis that resulted from a spontaneous mutation in a B6 Apc(Min)/+ mouse. The presence of one resistant Mom2(R) allele results in a significant reduction in small intestinal polyp number and colon polyp incidence in Apc(Min)/+ mice. Through linkage analysis, we previously localized Mom2 to a 14-cM region on mouse Chromosome (Chr) 18, distal to the Apc gene. This region is syntenic with human Chr 18q, which frequently undergoes loss of heterozygosity (LOH) in several human cancers, including colorectal cancer. Residing in this region are the Madh2 and Madh4 genes, which have both been implicated in human colorectal cancer. Based on meiotic recombinations within the Mom2 region in the derivation of our congenic animals, we have narrowed the location of the Mom2 locus and excluded Madh2, Madh4, and Madh7, as well as Mbd1, Mbd2, Dcc, and Tcf4, as candidates for the Mom2 gene.
authors.affiliation: Kimmel Cancer Center, Jefferson Medical College, Bluemle Life Science Building, Room 709, 233 South 10th Street, Philadelphia, Pennsylvania 19107-5541, USA.
authors.forename: Karen A
authors.initials: KA
authors.lastname: Silverman
authors.forename: Revati A
authors.initials: RA
authors.lastname: Koratkar
authors.forename: Linda D
authors.initials: LD
authors.lastname: Siracusa
authors.forename: Arthur M
authors.initials: AM
authors.lastname: Buchberg
mesh_terms: D000483:Alleles; D000818:Animals; D002874:Chromosome Mapping; D002887:Chromosomes, Human, Pair 18; D015179:Colorectal Neoplasms / Q000473:pathology; D003433:Crosses, Genetic; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D008040:Genetic Linkage; D005838:Genotype; D006801:Humans; D019656:Loss of Heterozygosity; D008540:Meiosis; D051379:Mice; D008957:Models, Genetic; D009154:Mutation; D010641:Phenotype; D011995:Recombination, Genetic; D051899:Smad2 Protein; D051901:Smad4 Protein; D051906:Smad7 Protein; D015534:Trans-Activators / Q000096:biosynthesis* / Q000235:genetics; D014407:Tumor Cells, Cultured
chemical_list: D004268:DNA-Binding Proteins; C497782:SMAD2 protein, human; C497796:SMAD4 protein, human; C497806:SMAD7 protein, human; D051899:Smad2 Protein; C497783:Smad2 protein, mouse; D051901:Smad4 Protein; C490810:Smad4 protein, mouse; D051906:Smad7 Protein; C497807:Smad7 protein, mouse; D015534:Trans-Activators