RPGR transcription studies in mouse and human tissues reveal a retina-specific isoform that is disrupted in a patient with X-linked retinitis pigmentosa.
X-linked retinitis pigmentosa (XLRP) is a genetically heterogeneous group of progressive retinal degenerations. The disease process is initiated by premature apoptosis of rod photoreceptor cells in the retina, which leads to reduced visual acuity and, eventually, complete blindness. Mutations in the retinitis pigmentosa GTPase regulator ( RPGR ), a ubiquitously expressed gene at the RP3 locus in Xp21.1, account for approximately 20% of all X-linked cases. We have analysed the expression of this gene by northern blot hybridization, cDNA library screening and RT-PCR in various organs from mouse and man. These studies revealed at least 12 alternatively spliced isoforms. Some of the transcripts are tissue specific and contain novel exons, which elongate or truncate the previously reported open reading frame of the mouse and human RPGR gene. One of the newly identified exons is expressed exclusively in the human retina and mouse eye and contains a premature stop codon. The deduced polypeptide lacks 169 amino acids from the C-terminus of the ubiquitously expressed variant, including an isoprenylation site. Moreover, this exon was found to be deleted in a family with XLRP. Our results indicate tissue-dependent regulation of alternative splicing of RPGR in mouse and man. The discovery of a retina-specific transcript may explain why phenotypic abberations in RP3 are confined to the eye.
Max-Planck-Institut für molekulare Genetik, Ihnestrasse 73, D-14195 Berlin, Germany. kirschne@mpimg-berlin-dahlem.mpg.de
R
R
Kirschner
T
T
Rosenberg
R
R
Schultz-Heienbrok
S
S
Lenzner
S
S
Feil
R
R
Roepman
F P
FP
Cremers
H H
HH
Ropers
W
W
Berger
D000328:Adult; D000818:Animals; D000831:Animals, Newborn; D001483:Base Sequence; D001766:Blindness / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D002460:Cell Line; D018076:DNA, Complementary / Q000737:chemistry / Q000235:genetics; D005091:Exons / Q000235:genetics; D005136:Eye Proteins; D005260:Female; D005500:Follow-Up Studies; D015870:Gene Expression; D005796:Genes / Q000235:genetics; D008040:Genetic Linkage; D006801:Humans; D007438:Introns / Q000235:genetics; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D020033:Protein Isoforms / Q000235:genetics*; D012313:RNA / Q000235:genetics / Q000378:metabolism; D012160:Retina / Q000378:metabolism* / Q000473:pathology; D012174:Retinitis Pigmentosa / Q000235:genetics* / Q000473:pathology; D017422:Sequence Analysis, DNA; D017384:Sequence Deletion; D012689:Sequence Homology, Nucleic Acid; D014018:Tissue Distribution; D014158:Transcription, Genetic; D014787:Vision Tests; D014960:X Chromosome / Q000235:genetics*
D002352:Carrier Proteins; D018076:DNA, Complementary; D005136:Eye Proteins; D020033:Protein Isoforms; C099929:RPGR protein, human; D012313:RNA