A NEW HUMAN HOMEOBOX GENE OG12X IS A MEMBER OF THE MOST CONSERVED HOMEOBOX GENE FAMILY AND IS EXPRESSED DURING HEART DEVELOPMENT IN MOUSE

Homeodomain (HD) proteins are transcription regulators controlling a v ariety of cell fates, The HD region characterizing this protein family is a domain of 60 amino acid residues that recognizes and binds a sit e in the regulatory region of the target gene, It has been suggested t hat regions outside the HD may determine the specific functions of the various HD proteins by forming additional contacts with DNA sequences or by interactions with other proteins, We have identified a 14 amino acid motif within the C-terminal region of the protein encoded by the RIEG1 gene that is conserved among several HD proteins, Overlapping e xpression of the genes encoding these proteins during craniofacial dev elopment suggested that they might interact with a common factor, In o rder to identify additional genes possessing this motif we screened a human craniofacial cDNA library with oligoprobes. A novel gene was ide ntified, exhibiting the most homology to murine Og12x (formerly OG12) and the recently reported human SHOX gene, Human OG12X and murine Og12 x are highly homologous and the OG12X and Og12x proteins are 100% iden tical, In situ hybridization on mouse embryos ranging from 9 to 16 day s post-coitum localized murine Og12x mRNA in the heart, otic region, m axillary and mandibular components of the first branchial arch, nasal processes, eyelid, midbrain, medulla oblongata, limbs, dorsal root gan glia and genital tubercle, OG12X was mapped to human chromosome 3q22-2 6 and murine Og12x to the syntenic region on mouse chromosome 3. Based upon the expression pattern of its mouse cognate, OG12X represents a candidate for the blepharophimosis (BPES) and Cornelia de Lange syndro mes previously mapped to this region.