Cloning, characterization and chromosome mapping of the human SOX6 gene.

The Sox gene family encodes an important group of transcription factors harboring the conserved high-mobility group (HMG) box originally identified in the mouse and human testis determining gene Sry. We have cloned and sequenced SOX6, a member of the human Sox gene family. SOX6 cDNAs isolated from a human myoblast cDNA library show 94.3% amino acid identity to mouse Sox6 throughout the gene, and 100% identity in the critical HMG box and coiled-coil domains. The human SOX6 gene was localized to chromosome 11p15.2-11p15.3 in a region of shared synteny with distal mouse chromosome 7. An analysis of the genomic structure of the human SOX6 gene revealed 16 exons. We identified three SOX6 cDNAs that are generated by alternative splicing. Northern blot analysis revealed that SOX6 is expressed in a wide variety of tissues, most abundantly in skeletal muscle, suggesting an important role for SOX6 in muscle. Mice homozygous for a null mutation of Sox6 (p(100H)) die suddenly within the first 2 weeks after birth, most likely from cardiac conduction defects (Hagiwara et al., 2000). Thus, there is a possibility that human SOX6 is similarly involved in an, as yet, unidentified human cardiac disorder.