Multiple Intestinal Neoplasia Caused by a Mutation in the Murine Homolog of the APC Gene

TLDR

Germ‑line APC mutations cause familial adenomatous polyposis, a dominantly inherited disease marked by multiple benign colorectal tumors, and analogous mutations are also found in sporadic colorectal cancers. A mouse line with an autosomal dominant predisposition to multiple intestinal neoplasia (Min) was linked to the murine APC homolog, where a nonsense mutation cosegregated with the phenotype.

Abstract

Germ-line mutations of the APC gene are responsible for familial adenomatous polyposis (FAP), an autosomal dominantly inherited disease in humans. Patients with FAP develop multiple benign colorectal tumors. Recently, a mouse lineage that exhibits an autosomal dominantly inherited predisposition to multiple intestinal neoplasia (Min) was described. Linkage analysis showed that the murine homolog of the APC gene (mApc) was tightly linked to the Min locus. Sequence comparison of mApc between normal and Min-affected mice identified a nonsense mutation, which cosegregated with the Min phenotype. This mutation is analogous to those found in FAP kindreds and in sporadic colorectal cancers.