Epithelial cancer in Fanconi anemia complementation group D2 (<i>Fancd2</i>) knockout mice
書誌事項
- 公開日
- 2003-07-31
- DOI
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- 10.1101/gad.1103403
- 公開者
- Cold Spring Harbor Laboratory
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説明
<jats:p>Fanconi anemia (FA) is a genetic disorder characterized by hypersensitivity to DNA damage, bone marrow failure, congenital defects, and cancer. To further investigate the in vivo function of the FA pathway, mice with a targeted deletion in the distally acting FA gene<jats:italic>Fancd2</jats:italic>were created. Similar to human FA patients and other FA mouse models,<jats:italic>Fancd2</jats:italic>mutant mice exhibited cellular sensitivity to DNA interstrand cross-links and germ cell loss. In addition, chromosome mispairing was seen in male meiosis. However,<jats:italic>Fancd2</jats:italic>mutant mice also displayed phenotypes not observed in other mice with disruptions of proximal FA genes. These include microphthalmia, perinatal lethality, and epithelial cancers, similar to mice with<jats:italic>Brca2/Fancd1</jats:italic>hypomorphic mutations. These additional phenotypes were not caused by defects in the ATM-mediated S-phase checkpoint, which was intact in primary<jats:italic>Fancd2</jats:italic>mutant fibroblasts. The phenotypic overlap between<jats:italic>Fancd2</jats:italic>-null and<jats:italic>Brca2/Fancd1</jats:italic>hypomorphic mice is consistent with a common function for both proteins in the same pathway, regulating genomic stability.</jats:p>
収録刊行物
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- Genes & Development
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Genes & Development 17 (16), 2021-2035, 2003-07-31
Cold Spring Harbor Laboratory