Disease relevance of CEP290

• Using genetic mapping and positional candidate strategy, we have identified an in-frame deletion in a novel centrosomal protein CEP290 (also called NPHP6), leading to early-onset retinal degeneration in a newly identified mouse mutant, rd16 [1].
• Using MAb 3H11, we screened cDNA library made from the human gastric cancer cell line MGC 803, which reacts with MAb 3H11, and isolated one positive clone specifically recognized by the antibody [2].
• Then, phage antibody library and random mutated library were constructed from 3H11 hybridoma cells and panning selection was perfomed [3].

High impact information on CEP290

• CEP290 expression was detected mostly in proliferating cerebellar granule neuron populations and showed centrosome and ciliary localization, linking JSRDs to other human ciliopathies [4].
• Mutations in CEP290, which encodes a centrosomal protein, cause pleiotropic forms of Joubert syndrome [4].
• NPHP6 is found at centrosomes and in the nucleus of renal epithelial cells in a cell cycle-dependent manner and in connecting cilia of photoreceptors [5].
• Mutations in the CEP290 (NPHP6) gene are a frequent cause of Leber congenital amaurosis [6].
• Our findings suggest a critical function for CEP290 in ciliary transport and provide insights into the mechanism of early-onset photoreceptor degeneration [1].

Biological context of CEP290

• Immunogold labeling studies demonstrate the redistribution of RPGR and of phototransduction proteins in the photoreceptors of rd16 retina [1].

Anatomical context of CEP290

• We demonstrate that CEP290 localizes primarily to centrosomes of dividing cells and to the connecting cilium of retinal photoreceptors [1].
• And sequentially extracting the nuclei of COS-7 cells transfected with 3H11Ag showed that it is a DNA- and nuclear matrix-associated protein [7].
• Biochemical, phenotypic and functional studies revealed that the 3H11 molecule appeared to be different from previously established molecules on the T cell surface [8].
• By indirect immunofluorescence microscopy we show that antibody 3H11 reacts with all epithelial basement membranes in the kidneys, testes, epididymis, prostate, uterus, oviduct, and ovary, as well as the smooth muscle cells, blood vessels, and nerves [9].
• In contrast to 3H11, which reacted with all vascular, subendothelial, and muscular basement membranes, 4E10 reacted only with the subendothelial basement membrane of capillaries and veins [9].

Analytical, diagnostic and therapeutic context of CEP290

• Molecular cloning of the antigen recognized by MAb 3H11 is important in studying tumor occurrence and in developing new biotherapy for cancer [2].
• Northern blot and RT-PCR showed that the mRNA of MAb 3H11 antigen was extensively distributed in embryonic tissue and in different cancerous tissues, but not in corresponding normal tissues [2].
• Comparing the expression of unmutated and mutated 3H11 Fab, we found that the sequence changes of the V region N terminus introduced by PCR may seriously affect antigen binding but not the expression of antibody [10].

References