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Science 3 October 1997:
Vol. 278. no. 5335, pp. 120 - 123
DOI: 10.1126/science.278.5335.120
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Reports

Rapid Colorectal Adenoma Formation Initiated by Conditional Targeting of the Apc Gene

Hiroyuki Shibata, Kaoru Toyama, Hisashi Shioya, Masaki Ito, Morihisa Hirota, Sumitaka Hasegawa, Hiroshi Matsumoto, Hiroshi Takano, Tetsu Akiyama, Kumao Toyoshima, Ryunosuke Kanamaru, Yumi Kanegae, Izumu Saito, Yusuke Nakamura, Kiyotaka Shiba, Tetsuo Noda *

Familial adenomatous polyposis coli (FAP) is a disease characterized by the development of multiple colorectal adenomas, and affected individuals carry germline mutations in the APC gene. With the use of a conditional gene targeting system, a mouse model of FAP was created that circumvents the embryonic lethality of Apc deficiency and directs Apc inactivation specifically to the colorectal epithelium. loxP sites were inserted into the introns around Apc exon 14, and the resultant mutant allele (Apc580S) was introduced into the mouse germline. Mice homozygous for Apc580S were normal; however, upon infection of the colorectal region with an adenovirus encoding the Cre recombinase, the mice developed adenomas within 4 weeks. The adenomas showed deletion of Apc exon 14, indicating that the loss of Apc function was caused by Cre-loxP-mediated recombination.

H. Shibata, M. Ito, M. Hirota, H. Takano, T. Noda, Department of Cell Biology, Cancer Institute, Toshima-ku, Tokyo 170, Japan, and CREST, Japan Science and Technology Corporation, Japan.
K. Toyama, H. Shioya, S. Hasegawa, H. Matsumoto, K. Shiba, Department of Cell Biology, Cancer Institute, Toshima-ku, Tokyo 170, Japan.
T. Akiyama, Department of Oncogene Research, Institute for Microbial Diseases, Osaka University, Suita, Osaka 565, Japan.
K. Toyoshima, Center for Adult Diseases, Osaka 537, Japan.
R. Kanamaru, Department of Clinical Oncology, Institute of Development, Aging and Cancer, Tohoku University, Sendai 980, Japan.
Y. Kanegae and I. Saito, Laboratory of Molecular Genetics, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108, Japan.
Y. Nakamura, Laboratory of Molecular Medicine, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108, Japan.
*   To whom correspondence should be addressed.

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Science. ISSN 0036-8075 (print), 1095-9203 (online)