DNA sequence comparison of human and mouse retinitis pigmentosa GTPase regulator (RPGR) identifies tissue-specific exons and putative regulatory elements

Retinitis pigmentosa 3 (RP3) is a progressive retinal degeneration due to m utations in the X-linked RPGR gene. Transcription studies in human and mous e tissues have revealed ubiquitously expressed transcripts and also an exce ptional high number of tissue-specific alternative splice variants. However , regulation of tissue-specific expression and splicing is unclear, but thi s is of particular interest as mutations in this ubiquitously expressed gen e lead to severe retinal degeneration, while other tissues are unaffected. To elucidate the conservation pattern of RPGR and to identify additional ti ssue-specific exons and putative regulatory elements we per-formed comparat ive genomic sequencing of the human and mouse RPGR gene. Each of the genes spans a region of nearly 59 kb, and all previously identified exons are con served between the two species. DNA sequence comparison identified 28 conse rved sequence elements (CSEs) in introns, upstream of exon 1, within the pr omotor region, and downstream of the most 3' exon. Some of the intronic CSE s flank tissue-specific exons and therefore may represent important regulat ory elements for alternative splicing. Comparative northern blot hybridizat ion of ubiquitous and tissue-specific RPGR probes identified high molecular weight transcripts with similar expression patterns in both human and mous e. These transcripts range from 6 to 15 kb in size and suggest the presence of additional transcribed sequences within RPGR. Our cross-species sequenc e comparison enables us to define candidate regions that may explain these large transcripts and will therefore contribute to the understanding of RPG R expression and splicing.