In:
Cancer Science, Wiley, Vol. 104, No. 7 ( 2013-07), p. 937-944
Abstract:
Mutant mouse models are indispensable tools for clarifying the functions of genes and elucidating the underlying pathogenic mechanisms of human diseases. We carried out large‐scale mutagenesis using the chemical mutagen N ‐ethyl‐ N ‐nitrosourea. One specific aim of our mutagenesis project was to generate novel cancer models. We screened 7012 animals for dominant traits using a necropsy test and thereby established 17 mutant lines predisposed to cancer. Here, we report on a novel cancer model line that developed osteoma, trichogenic tumor, and breast cancer. Using fine mapping and genomic sequencing, we identified a point mutation in the adenomatous polyposis coli ( A pc ) gene. The A pc 1576 mutants bear a nonsense mutation at codon 1576 in the A pc gene. Although most A pc mutant mice established thus far have multifocal intestinal tumors, mice that are heterozygous for the A pc 1576 mutation do not develop intestinal tumors; instead, they develop multifocal breast cancers and trichogenic tumors. Notably, the osteomas that develop in the A pc 1576 mutant mice recapitulate the lesion observed in Gardner syndrome, a clinical variant of familial adenomatous polyposis. Our A pc 1576 mutant mice will be valuable not only for understanding the function of the A pc gene in detail but also as models of human Gardner syndrome.
Type of Medium:
Online Resource
ISSN:
1347-9032
,
1349-7006
DOI:
10.1111/cas.2013.104.issue-7
Language:
English
Publisher:
Wiley
Publication Date:
2013
detail.hit.zdb_id:
2115647-5
detail.hit.zdb_id:
2111204-6
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