| First Author | Pulliam-Leath AC | Year | 2010 |
| Journal | Blood | Volume | 116 |
| Issue | 16 | Pages | 2915-20 |
| PubMed ID | 20606166 | Mgi Jnum | J:165874 |
| Mgi Id | MGI:4838713 | Doi | 10.1182/blood-2009-08-240747 |
| Citation | Pulliam-Leath AC, et al. (2010) Genetic disruption of both Fancc and Fancg in mice recapitulates the hematopoietic manifestations of Fanconi anemia. Blood 116(16):2915-20 |
| abstractText | Fanconi anemia (FA) is an inherited chromosomal instability syndrome characterized by bone marrow failure, myelodysplasia (MDS), and acute myeloid leukemia (AML). Eight FA proteins associate in a nuclear core complex to monoubiquitinate FANCD2/FANCI in response to DNA damage. Additional functions have been described for some of the core complex proteins; however, in vivo genetic proof has been lacking. Here we show that double-mutant Fancc(-/-);Fancg(-/-) mice develop spontaneous hematologic sequelae including bone marrow failure, AML, MDS and complex random chromosomal abnormalities that the single-mutant mice do not. This genetic model provides evidence for unique core complex protein function independent of their ability to monoubiquitinate FANCD2/FANCI. Importantly, this model closely recapitulates the phenotypes found in FA patients and may be useful as a preclinical platform to evaluate the molecular pathogenesis of spontaneous bone marrow failure, MDS and AML in FA. |
