RAPID COLORECTAL ADENOMA FORMATION INITIATED BY CONDITIONAL TARGETINGOF THE APC GENE

Familial adenomatous polyposis coli (FAP) is a disease characterized b y the development of multiple colorectal adenomas, and affected indivi duals carry germline mutations in the APC gene. With the use of a cond itional gene targeting system, a mouse model oi FAP was created that c ircumvents the embryonic lethality of Apc deficiency and directs Apc i nactivation specifically to the colorectal epithelium. loxP sites were inserted into the introns around Ape exon 14, and the resultant mutan t allele (Apc(580S)) was introduced into the mouse germline. Mice homo zygous for Apc0(580S) were normal; however, upon infection of the colo rectal region with an adenovirus encoding the Cre recombinase, the mic e developed adenomas within 4 weeks, The adenomas showed deletion of A pc exon 14, indicating that the loss of Apc function was caused by Cre -loxP-mediated recombination.