Isolation and characterization of the murine X-linked juvenile retinoschisis (Rs1h) gene.

X-linked juvenile retinoschisis (RS) is a vitreoretinal degeneration affecting only males. Recently, the RS1 gene underlying this common cause of early 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 conserved discoidin motif at the C-terminus. Functional studies in other proteins with discoidin motifs have implicated this domain in phospholipid binding and cell-cell interactions on membrane surfaces. Thus, similar functional properties may exist for RS1 and may be related to the histopathological findings in RS. In order to further pursue the pathophysiology of RS and to understand RS1 function in early eye development, we now report the identification and characterization of the complete murine Rs1h gene. The full-length Rs1h cDNA was isolated by RT-PCR with degenerate oligonucleotide primers designed from human RS1 cDNA sequences. Subsequently, the exon/intron structure was determined in genomic DNA from mouse strain 129/SvJ. We show that human and murine RS1 coding sequences, exon/intron boundaries, as well as retina-specific expression, are highly conserved between the two species. The conceptual human and murine protein sequences reveal 96% amino acid identity with no amino acid changes within the discoidin domain. In addition, alignment of 5'-flanking sequences upstream of the human and mouse RS1 translation initiation sites identified putative binding sites for several transcription factors including CRX, a homeodomain transcription factor known to activate the transcription of several photoreceptor-specific genes.