期刊
BLOOD
卷 116, 期 16, 页码 2915-2920出版社
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2009-08-240747
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资金
- National Institutes of Health (Bethesda, MD) [NIH-NHLBI/P01 HL053586-14, NIH-NCI/R01 CA138287-01, T32 HL07910-09]
- DFG [SPP 1230]
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. (Blood.2010;116(16):2915-2920)
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