Fanconi anemia (FA) is a rare autosomal recessive disease, characterized by bone 
marrow failure and cancer predisposition. So far, 8 complementation groups have 
been identified, although mutations in FANCA account for the disease in the 
majority of FA patients. In this study we characterized the hematopoietic 
phenotype of a Fanca knockout mouse model and corrected the main phenotypic 
characteristics of the bone marrow (BM) progenitors using retroviral vectors. 
The hematopoiesis of these animals was characterized by a modest though 
significant thrombocytopenia, consistent with reduced numbers of BM 
megakaryocyte progenitors. As observed in other FA models, the hematopoietic 
progenitors from Fanca(-/-) mice were highly sensitive to mitomycin C (MMC). In 
addition, we observed for the first time in a FA mouse model a marked in vitro 
growth defect of Fanca(-/-) progenitors, either when total BM or when purified 
Lin(-)Sca-1(+) cells were subjected to in vitro stimulation. Liquid cultures of 
Fanca(-/-) BM that were stimulated with stem cell factor plus interleukin-11 
produced low numbers of granulocyte macrophage colony-forming units, contained a 
high proportion of apoptotic cells, and generated a decreased proportion of 
granulocyte versus macrophage cells, compared to normal BM cultures. Aiming to 
correct the phenotype of Fanca(-/-) progenitors, purified Lin(-)Sca-1(+) cells 
were transduced with retroviral vectors encoding the enhanced green fluorescent 
protein (EGFP) gene and human FANCA genes. Lin(-)Sca-1(+) cells from Fanca(-/-) 
mice were transduced with an efficiency similar to that of samples from 
wild-type mice. More significantly, transductions with FANCA vectors corrected 
both the MMC hypersensitivity as well as the impaired ex vivo expansion ability 
that characterized the BM progenitors of Fanca(-/-) mice.