title: Microadenomatous lesions involving loss of Apc heterozygosity in the colon of adult Apc(Min/+) mice.
abstract: Mutations in the human adenomatous polyposis coli (APC) gene are causative for familial adenomatous polyposis (FAP), a rare condition in which numerous colonic polyps arise during puberty and, if left untreated, lead to colon cancer. Mouse model for human FAP, Apc(Min/+) mouse, contains a truncating mutation in the Apc gene and spontaneously develops intestinal adenomas. However, the distribution of tumors along the intestine found in Apc(Min/+) mice is different from that in human FAP. A majority of intestinal polyps in the Apc(Min/+) mice is known to be located in the small intestine but rarely detected in the colon. We report here that adult Apc(Min/+) mice develop dozens of microadenomatous lesions in the colon (>20 lesions/colon). Surprisingly, the vast majority of such adenomatous lesions consisting of colonic crypts were <300 microm in their greatest dimension, whereas lesions in the small intestine showed various sizes. The allelic loss analysis revealed that these adenomatous crypts in the colon have already lost the remaining allele of Apc. Such findings suggest that, in contrast to tumorigenesis in the small intestine, loss of heterozygosity of the Apc gene is not sufficient for tumor development in the colon of Apc(Min/+) mice. Our results may give an account for the low incidence of colonic tumors in Apc(Min/+) mice.
authors.affiliation: Department of Pathology, Gifu University School of Medicine, Gifu 500-8705, Japan. : y-yamada@cc.gifu-u.ac.jp
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Yamada
authors.forename: Kazuya
authors.initials: K
authors.lastname: Hata
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Hirose
authors.forename: Akira
authors.initials: A
authors.lastname: Hara
authors.forename: Shigeyuki
authors.initials: S
authors.lastname: Sugie
authors.forename: Toshiya
authors.initials: T
authors.lastname: Kuno
authors.forename: Naoki
authors.initials: N
authors.lastname: Yoshimi
authors.forename: Takuji
authors.initials: T
authors.lastname: Tanaka
authors.forename: Hideki
authors.initials: H
authors.lastname: Mori
mesh_terms: D011125:Adenomatous Polyposis Coli / Q000235:genetics* / Q000473:pathology; D000483:Alleles; D000818:Animals; D005260:Female; D017491:Genes, APC / Q000502:physiology*; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000473:pathology; D007421:Intestine, Small / Q000473:pathology; D019656:Loss of Heterozygosity; D051379:Mice