| First Author | Hadjur S | Year | 2001 |
| Journal | Blood | Volume | 98 |
| Issue | 4 | Pages | 1003-11 |
| PubMed ID | 11493445 | Mgi Jnum | J:71134 |
| Mgi Id | MGI:2149223 | Doi | 10.1182/blood.v98.4.1003 |
| Citation | Hadjur S, et al. (2001) Defective hematopoiesis and hepatic steatosis in mice with combined deficiencies of the genes encoding Fancc and Cu/Zn superoxide dismutase. Blood 98(4):1003-11 |
| abstractText | Several lines of evidence point to an abnormality in the response of Fanconi anemia cells to reactive oxygen species. To investigate the potential pathologic consequences of an in vivo alteration of redox state in mice lacking one of the Fanconi anemia genes, animals were generated having combined deficiencies of the cytosolic Cu/Zn superoxide dismutase (Sod1) and Fanconi anemia complementation group C (Fancc) genes. Interestingly, hepatocytes of Fancc(-/-)Sod1(-/-) mice exhibited a zonal pattern of microvesicular steatosis, possibly as a result of oxidative stress-induced injury to hepatocyte membranes. Consistent with this idea, freshly explanted Fancc(-/-)Sod1(-/-) hepatocytes demonstrated increased spontaneous production of superoxide in vitro. The second phenotypic feature of Fancc(-/-) Sod1(-/-) mice was that of bone marrow hypocellularity accompanied by significant decreases in peripheral blood erythrocyte and leukocyte numbers as compared with wild-type controls. Although flow cytometry analysis with monoclonal antibodies against cell surface antigens revealed normal numbers of primitive hematopoietic progenitor populations in Fancc(-/-)Sod1(-/-) marrow, lineage-positive progenitor numbers were significantly reduced in these mice. Furthermore, the in vitro clonogenic growth of Fancc(-/-)Sod1(-/-) erythroid, myeloid, and early B-lymphoid colonies in semisolid media was profoundly compromised. These results suggested that the altered redox state likely present in Fancc(-/-) Sod1(-/-) hematopoietic progenitors was responsible for an impairment of cell proliferation or survival. (Blood. 2001;98:1003-1011) |
