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

与癌症相关视网膜病变相对应的新视网膜自身抗原基因的特征

基本信息

批准号：
11671728
负责人：
KIKUCHI Takanobu
金额：
$ 2.24万
依托单位：
SHINSHU UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2000
项目状态：
已结题

项目摘要

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.

癌症相关性视网膜病变(CAR)是一种罕见的视网膜变性，也是副肿瘤性神经系统疾病之一。CAR患者的血清通常含有高滴度的视网膜蛋白抗体，CAR被认为是一种自身免疫性疾病。以CAR患者血清为分子探针，从新生大鼠视网膜的cDNA文库中分离到多嘧啶结合蛋白(PTB)的同源基因。该同源物命名为PTB样蛋白(PTBLP)，编码532个氨基酸残基，与PTB和分化调节因子1的同源性分别为73.5%和68.8%。PTB中的功能区，如核定位信号和四个RNA识别基序(RRMS)高度保守。PTBLP基因在视网膜和脑中有表达，而在肝、肾、脾和肺中未见表达。PTBLP蛋白在大鼠视网膜中的表达主要分布在神经节细胞层的大部分细胞和内核层的部分细胞。PTBLP蛋白定位于这些细胞的细胞核中。这些结果表明，PTBLP是PTB基因家族的新成员，是神经元特异性同源物。CAR血清识别PTBLP，PTBLP的抗原决定簇定位在C-末端的12个氨基酸内。该多肽序列包括在第四个RRM序列中。