Isolation and characterization of the murine X-linked juvenile retinoschisis (Rslh) gene

X-linked juvenile retinoschisis (RS) is a vitreoretinal degeneration affect ing only males. Recently, the RS1 gene underlying this common cause of earl y vision loss was identified and shown to encode a 224-amino acid precursor protein including a 23-residue leader sequence as well as a highly conserv ed discoidin motif at the C-terminus. Functional studies in other proteins with discoidin motifs have implicated this domain in phospholipid binding a nd cell-cell interactions on membrane surfaces. Thus, similar functional pr operties may exist for RS1 and may be related to the histopathological find ings in RS. In order to further pursue the pathophysiology of RS and to und erstand RS1 function in early eye development, we now report the identifica tion and characterization of the complete murine Rs1h gene. The full-length Rs1h cDNA was isolated by RT-PCR with degenerate oligonucleotide primers d esigned from human RS1 cDNA sequences. Subsequently, the exon/intron struct ure was determined in genomic DNA from mouse strain 129/SvJ. We show that h uman and murine RS1 coding sequences, exon/intron boundaries, as well as re tina-specific expression, are highly conserved between the two species. The conceptual human and murine protein sequences reveal 96% amino acid identi ty with no amino acid changes within the discoidin domain. In addition, ali gnment of 5'-flanking sequences upstream of the human and mouse RS1 transla tion initiation sites identified putative binding sites for several transcr iption factors including CRX, a homeodomain transcription factor known to a ctivate the transcription of several photoreceptor-specific genes.