Cloning and analysis of the mouse Fanconi anemia group a cDNA and an overlapping penta zinc finger cDNA

Despite the cloning of four disease-associated genes for Fanconi anemia (FA ), the molecular pathogenesis of FA remains largely unknown. To study FA co mplementation group A using the mouse as a mode I system, we cloned and cha racterized the mouse homolog of the human FANCA cDNA, The mouse cDNA (Fanca ) encodes a 161-kDa protein that shares 65% amino acid sequence identity wi th human FANCA. Fanca is located at the distal region of mouse chromosome 8 and has a ubiquitous pattern of expression in embryonic and adult tissues. Expression of the mouse DNA in human FA-A cells restores the cellular drug sensitivity to normal levels. Thus, the expression pattern, protein struct ure, chromosomal location, and function of FANCA are conserved in the mouse . We also isolated a novel zinc finger protein, Zfp276, which has five C2H2 domains. Interestingly, Zfp276 is situated in the Fanca locus, and the 3'U TR of its cDNA overlaps with the last four exons of Fanca in a tail-to-tail manner. Zfp276 is expressed in the same tissues as Fanca, but does not com plement the mitomycin C (MMC)-sensitive phenotype of FA-A cells. The overla pping genomic organization between Zfp276 and Fanca may have relevance to t he disease phenotype of FA. (C) 2000 Academic Press.