Mice with a targeted disruption of the Fanconi anemia homolog Fanca

Fanconi anemia (FA) is a hereditary chromosomal instability syndrome with c ancer predisposition. Bone marrow failure resulting in pancytopenia is the main cause of death of FA patients. Diagnosis of FA is based on their cellu lar hypersensitivity to DNA crosslinking agents and chromosome breakages. S omatic complementation experiments suggest the involvement of at least eigh t genes in FA, The gene for complementation group A (FANCA) is defective in the majority of FA patients. We show here that mice deficient of Fanca are viable and have no detectable developmental abnormalities. The hematologic al parameters showed a slightly decreased platelet count and a slightly inc reased erythrocyte mean cell volume in mice at young age, but this did not progress to anemia. Consistent with the clinical phenotype of FA patients, both male and female mice showed hypogonadism and impaired fertility. Furth ermore, embryonic fibroblasts of the knock-out mice exhibited spontaneous c hromosomal instability and were hyper-responsive to the clastogenic effect of the crosslinker mitomycin C.