Epithelial cancer in Fanconi anemia complementation group D2 (Fancd2) knockout mice

Scott Houghtaling, Cynthia Timmers, Meenakshi Noll, Milton J. Finegold, Stephen N. Jones, M. Stephen Meyn, Markus Grompe

Research output: Contribution to journalArticlepeer-review

219 Scopus citations


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 Fancd2 were created. Similar to human FA patients and other FA mouse models, Fancd2 mutant mice exhibited cellular sensitivity to DNA interstrand cross-links and germ cell loss. In addition, chromosome mispairing was seen in male meiosis. However, Fancd2 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 Brca2/Fancd1 hypomorphic mutations. These additional phenotypes were not caused by defects in the ATM-mediated S-phase checkpoint, which was intact in primary Fancd2 mutant fibroblasts. The phenotypic overlap between Fancd2-null and Brca2/Fancd1 hypomorphic mice is consistent with a common function for both proteins in the same pathway, regulating genomic stability.

Original languageEnglish (US)
Pages (from-to)2021-2035
Number of pages15
JournalGenes and Development
Issue number16
StatePublished - Aug 15 2003


  • Brca2
  • Cancer
  • Chromosome pairing
  • DNA repair
  • Fancd2
  • Fanconi anemia

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology


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