GENOMIC STRUCTURE OF A NOVEL LIM DOMAIN GENE (ZNF185) IN XQ28 AND COMPARISONS WITH THE ORTHOLOGOUS MURINE TRANSCRIPT

Construction of a transcript map in the DXS52 region in Xq28 had previ ously led to the isolation of a cDNA with a LIM zinc finger domain in the carboxyl terminus. In parallel, the orthologous murine transcript was isolated from the syntenic region. The human and mouse cDNAs have been designated ZNF185 and Zfp185, respectively. By integrating the cD NA sequence with the cosmid derived genomic sequence the exon-intron s tructure of the 3' end of the ZNF185 gene was resolved. Comparative se quence analyses of the human genomic sequence with the full-length mur ine cDNA facilitated prediction of the 5' end of the gene. The selecti ve expression of three transcripts corresponding to the ZNF185 gene an d a related gene was shown by Northern and Southern blots. In situ hyb ridizations revealed a nonubiquitous and stage-specific expression of Zfp185, especially in differentiating connective tissue. Since LIM pro teins regulate cellular proliferation and/or differentiation by divers e mechanisms, and some have directly been associated with disease, con ceivably ZNF185 may represent a candidate for a disease-causing gene l inked to Xq28. Knowledge of the genomic structure will permit detailed mutation analyses. (C) 1997 Academic Press.