Cloning and characterization of murine Fanconi anemia group A gene: Fanca protein is expressed in lymphoid tissues, testis, and ovary

Fanconi anemia (FA) is an autosomal recessive disorder in humans characteri zed by bone narrow failure, cancer predisposition, and cellular hypersensit ivity to cross-linking agents such as mitomycin C and diepoxybutane. FA gen es display a caretaker function essential for maintenance of genomic integr ity. We have cloned the murine homolog of FANCA, the gene mutated in the ma jor FA complementation group (FA-A). The full-length mouse Fanca cDNA consi sts of 4503 bp and encodes a protein with a predicted molecular weight of 1 61 kDa. The deduced Fanca mouse protein shares 81% amino acid sequence simi larity and 66% identity with the human protein. The nuclear localization si gnal and partial leucine zipper consensus motifs found in the human FANCA p rotein were also present in the murine homolog. In spite of the species dif ference, the murine Fanca cDNA was capable of correcting the cross-linker s ensitive phenotype of human FA-A cells, suggesting functional conservation. Based on Northern as well as Western blots, Fanca was mainly expressed in lymphoid tissues, testis, and ovary. This expression pattern correlates wit h some of the clinical symptoms observed in FA patients. The availability o f the murine Fanca cDNA now allows the gene to be studied in experimental m ouse models.