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[Cancer Research 59, 1301-1307, March 1, 1999]
© 1999 American Association for Cancer Research
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[Cancer Research 59, 1301-1307, March 15, 1999]
© 1999 American Association for Cancer Research

Molecular Biology and Genetics

Tumorigenesis in Mlh1 and Mlh1/Apc1638N Mutant Mice1

Winfried Edelmann2,,3, Kan Yang2, Mari Kuraguchi, Joerg Heyer, Marie Lia, Burkhard Kneitz, Kunhua Fan, Anthony M. C. Brown, Martin Lipkin and Raju Kucherlapati4

Department of Molecular Genetics, Albert Einstein College of Medicine, Bronx, New York 10461 [W. E., J. H., M. Lia, B. K., R. K.]; and Strang Cancer Prevention Center [K. Y., M. K., K. F., A. M. C. B., M. Lip.] and Department of Cell Biology and Anatomy, Cornell University Medical College [A. M. C. B.], New York, New York 10021

ABSTRACT

MutL homologue 1 (MLH1) is a member of the family of proteins required for DNA mismatch repair. Germ-line mutations in MLH1 lead to the cancer susceptibility syndrome hereditary nonpolyposis colorectal cancer (HNPCC). We generated mice carrying a null mutation in the Mlh1 gene. We showed that mice heterozygous and homozygous for the Mlh1 gene are predisposed to developing tumors of the gastrointestinal (GI) tract, lymphomas, and a number of other tumor types. We also examined the role of adenomatous polyposis coli gene (Apc) gene mutations in the GI tumors of Mlh1 mutant mice by different methods and showed that the GI tumors in Mlh1 mice express little or no adenomatous polyposis coli protein. When an Apc gene mutation was bred into the Mlh1 mutant mice, the GI tumor incidence increased 40–100-fold. The wild-type Apc allele in these tumors was found to contain mutations. Together, these results show that we have developed two mouse models for human HNPCC and that the mechanisms of tumor development in the GI tract of these mice involve loss of Apc gene function in a manner very similar to that seen in the GI tumors of HNPCC.




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HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Meeting Abstracts Online
Copyright © 1999 by the American Association for Cancer Research.