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1 From the F. M. Kirby Center for Molecular Ophthalmology and the 5 Scheie Eye Institute, University of Pennsylvania, Philadelphia, Pennsylvania; the 2 Human Genetics Center, School of Public Health, and the Department of Ophthalmology and Visual Science, The University of Texas Health Science Center, Houston, Texas; the 4 Jules Stein Eye Institute, University of California School of Medicine, Los Angeles, California; and the 6 Department of Developmental Neurobiology, St. Jude Children’s Research Hospital, Memphis, Tennessee.
PURPOSE. Mutations in the RP1 gene account for 6% to 10% of autosomal dominant retinitis pigmentosa (adRP). Previous studies have shown that the RP1 gene is expressed specifically in photoreceptor cells. So far, little is known about the RP1 protein or how mutations in RP1 lead to photoreceptor cell death. The goal of this study was to identify the RP1 protein and investigate its location in photoreceptor cells.
METHODS. A combination of RT-PCR and rapid amplification of cDNA ends (RACE) was used to isolate the full-length mouse Rp1 cDNA. Antibodies against different regions of the predicted mouse Rp1 protein were generated. Western blot analyses were used to identify the RP1/Rp1 proteins. The subcellular location of RP1 in human and mouse retinas was determined by immunostaining retinal sections.
RESULTS. The full-length mouse Rp1 cDNA is 6944 bp, encoding a predicted protein of 2095 amino acids. Rp1 was found to be a soluble protein of approximately 240 kDa, consistent with predictions based on the cDNA sequence. Immunofluorescence analyses revealed that both the human RP1 and mouse Rp1 proteins are specifically localized in the connecting cilia of rod and cone photoreceptors.
CONCLUSIONS. The presence of RP1/Rp1 in connecting cilia suggests that it may participate in transport of proteins between the inner and outer segments of photoreceptors or in maintenance of cilial structure. This study forms the basis for further investigation of the function of RP1 in retina and the mechanism by which mutations in RP1 lead to photoreceptor cell death.
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