BIOCHEMICAL-CHARACTERIZATION AND SUBCELLULAR-LOCALIZATION OF THE MOUSE RETINITIS-PIGMENTOSA GTPASE REGULATOR (MRPGR)

The retinitis pigmentosa GTPase regulator (RPGR) gene encodes a protei n homologous to the RCC1 guanine nucleotide exchange factor and is mut ated in 20% of patients with X-linked retinitis pigmentosa, We have ch aracterized the fall-length and variant cDNAs corresponding to the mou se homolog of the RPGR gene (mRpgr), Comparison with the human cDNA re vealed sequence identity primarily in the region of RCC1 homology repe ats. As in humans, the mRpgr gene maps within 50 kilobases from the 5' -end of the Otc gene. The mRpgr transcripts are detected as early as E 7 during embryonic development and are expressed widely in the adult m ice. Variant mRpgr isoforms are generated by alternative splicing and by utilizing two in-frame initiation codons, The products of mRpgr cDN As migrate aberrantly in SDS-polyacrylamide gels because of a charged domain. In transfected COS cells, the mRpgr protein is isoprenylated a nd is localized in the Golgi complex. This subcellular distribution is not observed after treatments with brefeldin A or mevastatin and when the conserved isoprenylation sequence (CTIL) at the carboxyl terminus is deleted or mutagenized, These studies suggest a role for the mRpgr protein in Golgi transport and form the basis for investigating the m echanism of photoreceptor degeneration in X-linked retinitis pigmentos a.