A targeted chain-termination mutation in the mouse Apc gene results in multiple intestinal tumors

Riccardo Fodde, Winfried Edelmann, Kan Yang, Claus Van Leeuwen, Christine Carlson, Beatrice Renault, Cor Breukel, Elaine Alt, Martin Lipkin, P. Meera Khan, Raju Kucherlapati

Research output: Contribution to journalArticle

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Abstract

Germ-line mutations in the human adenomatous polyposis coli (APC) gene result in familial adenomatous polyposis, an autosomal dominant disorder characterized by the early onset of multiple adenomatous polyps in the large bowel with a high likelihood of developing colorectal carcinomas. To understand the role of APC in intestinal tumor formation, we have introduced a chain-termination mutation in the 15th exon of the mouse Apc gene and employed it to modify the endogenous gene by homologous recombination in embryonic stem cells. Mice which are heterozygous for the Apc gene modification progressively develop intestinal tumors in a manner that is similar to that observed in patients with familial adenomatous polyposis and in mice which carry a mutation called multiple intestinal neoplasia (Min). Our results indicate that the Apc gene modification is a critical event in the initiation of intestinal tumor formation and results in an autosomal dominant predisposition toward development of spontaneous colonic and intestinal tumors in mice.

Original languageEnglish (US)
Pages (from-to)8969-8973
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume91
Issue number19
DOIs
StatePublished - Sep 13 1994

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Adenomatous Polyposis Coli
Mutation
Genes
Neoplasms
APC Genes
Adenomatous Polyps
Germ-Line Mutation
Homologous Recombination
Embryonic Stem Cells
Colorectal Neoplasms
Exons

Keywords

  • animal model for human disease
  • colorectal cancer
  • gene targeting

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

A targeted chain-termination mutation in the mouse Apc gene results in multiple intestinal tumors. / Fodde, Riccardo; Edelmann, Winfried; Yang, Kan; Van Leeuwen, Claus; Carlson, Christine; Renault, Beatrice; Breukel, Cor; Alt, Elaine; Lipkin, Martin; Khan, P. Meera; Kucherlapati, Raju.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 91, No. 19, 13.09.1994, p. 8969-8973.

Research output: Contribution to journalArticle

Fodde, R, Edelmann, W, Yang, K, Van Leeuwen, C, Carlson, C, Renault, B, Breukel, C, Alt, E, Lipkin, M, Khan, PM & Kucherlapati, R 1994, 'A targeted chain-termination mutation in the mouse Apc gene results in multiple intestinal tumors', Proceedings of the National Academy of Sciences of the United States of America, vol. 91, no. 19, pp. 8969-8973. https://doi.org/10.1073/pnas.91.19.8969
Fodde, Riccardo ; Edelmann, Winfried ; Yang, Kan ; Van Leeuwen, Claus ; Carlson, Christine ; Renault, Beatrice ; Breukel, Cor ; Alt, Elaine ; Lipkin, Martin ; Khan, P. Meera ; Kucherlapati, Raju. / A targeted chain-termination mutation in the mouse Apc gene results in multiple intestinal tumors. In: Proceedings of the National Academy of Sciences of the United States of America. 1994 ; Vol. 91, No. 19. pp. 8969-8973.
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