The pleiotropic phenotype of apc mutations in the mouse: allele specificity and effects of the genetic background.

The pleiotropic phenotype of apc mutations in the mouse: allele specificity and effects of the genetic background. Research Abstract Details 

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The pleiotropic phenotype of apc mutations in the mouse: allele specificity and effects of the genetic background. Abstract Text:

Familial adenomatous polyposis (FAP) is a human cancer syndrome characterized by the development of hundreds to thousands of colonic polyps and extracolonic lesions including desmoid fibromas, osteomas, epidermoid cysts, and congenital hypertrophy of the pigmented retinal epithelium. Afflicted individuals are heterozygous for mutations in the APC gene. Detailed investigations of mice heterozygous for mutations in the ortholog Apc have shown that other genetic factors strongly influence the phenotype. Here we report qualitative and quantitative modifications of the phenotype of Apc mutants as a function of three genetic variables: Apc allele, p53 allele, and genetic background. We have found major differences between the Apc alleles Min and 1638N in multiplicity and regionality of intestinal tumors, as well as in incidence of extracolonic lesions. By contrast, Min mice homozygous for either of two different knockout alleles of p53 show similar phenotypic effects. These studies illustrate the classic principle that functional genetics is enriched by assessing penetrance and expressivity with allelic series. The mouse permits study of an allelic gene series on multiple genetic backgrounds, thereby leading to a better understanding of gene action in a range of biological processes.

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The pleiotropic phenotype of apc mutations in the mouse: allele specificity and effects of the genetic background. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Genetics

VOLUME: 180

Page Numbers: 601-9

Journal Abbreviation: Genetics

ISSN: 0016-6731

DAY: 24

MONTH: 08

YEAR: 2008

The pleiotropic phenotype of apc mutations in the mouse: allele specificity and effects of the genetic background. Information

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LANGUAGE: eng

NlmUniqueID: 374636

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Grant and Affiliation Information for The pleiotropic phenotype of apc mutations in the mouse: allele specificity and effects of the genetic background.

AFFILIATION: Laboratory of Genetics, University of Wisconsin, Madison, Wisconsin 53706.

Country: United States

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MEDLINETA: Genetics

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