Targeted mutations of breast cancer susceptibility gene homologs in mice: lethal phenotypes of Brca1, Brca2, Brca1/Brca2, Brca1/p53, and Brca2/p53 nullizygous embryos.

Genes and Development - Tập 11 Số 10 - Trang 1226-1241 - 1997
Thomas Ludwig1, Deborah L. Chapman1, Virginia E. Papaioannou1, Argiris Efstratiadis1
1Departments of 1Anatomy and Cell Biology and ~Genetics and Development, Columbia University, New York, New York 10032 USA

Tóm tắt

Mutations of the human BRCA1 and BRCA2 genes encoding tumor suppressors have been implicated in inherited predisposition to breast and other cancers. Disruption of the homologous mouse genes Brca1 and Brca2 by targeting showed that they both have indispensable roles during embryogenesis, because nullizygous embryos become developmentally retarded and disorganized, and die early in development. In Brca1 mutants, the onset of abnormalities is earlier by one day and their phenotypic features and time of death are highly variable, whereas the phenotype of Brca2 null embryos is more uniform, and they all survive for at least 8.5 embryonic days. Observations with Brca1/Brca2 double nullizygotes raise the possibility that the two developmental pathways could be linked. Interestingly, the impact of the Brca1 or Brca2 null mutation is less severe in a p53 null background.

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Genes and Development

Tập 11 Số 10

1226-1241

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