CHARACTERIZATION OF A NEW RETINAL AUTOANTIGEN GENE CORRESPONDING WITH CANCER-ASSOCIATED RETINOPATHY

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Cancer-associated retinopathy (CAR) is a rare form of retinal degeneration and also one of the paraneoplastic neurologic disorders. Sera of CAR patients usually contain high titers of antibodies against retinal proteins, and CAR is believed to be an autoimmune disease. Using serum from a CAR patient as a molecular probe, a homologue of the polypyrimidine tract binding protein (PTB) was isolated from a cDNA library of rat neonatal retina. This homologue, named PTB-like protein (PTBLP), encodes a 532 amino acid residue protein, and has 73.5% and 68.8% homology with PTB and with a regulator of differentiation 1, respectively. Functional domains in the PTB, such as nuclear localization signals and four RNA recognition motifs (RRMs), were highly conserved. The expression of PTBLP mRNA was observed in the retina and brain but not in liver, kidney, spleen or lung. The expression of PTBLP protein in rat retina was distributed to most of the cells in the ganglion cell layer and some cells in the inner nuclear layer. The PTBLP protein was localized in the nuclei of these cells. These results suggest that PTBLP is a new member of the PTB gene family and is a neuron-specific homologue. CAR serum recognized the PTBLP, the antigenic determinant of the PTBLP was localized within 12 amino acids of the C-terminal region. The sequence of the peptide was included in the fourth RRM sequence.