| First Author | Ronquillo CC | Year | 2016 |
| Journal | FASEB J | Volume | 30 |
| Issue | 10 | Pages | 3400-3412 |
| PubMed ID | 27328943 | Mgi Jnum | J:239714 |
| Mgi Id | MGI:5829530 | Doi | 10.1096/fj.201600511R |
| Citation | Ronquillo CC, et al. (2016) Ciliopathy-associated IQCB1/NPHP5 protein is required for mouse photoreceptor outer segment formation. FASEB J 30(10):3400-3412 |
| abstractText | Null mutations in the human IQCB1/NPHP5 (nephrocystin-5) gene that encodes NPHP5 are the most frequent cause of Senior-Loken syndrome, a ciliopathy that is characterized by Leber congenital amaurosis and nephronophthisis. We generated germline Nphp5-knockout mice by placing a beta-Geo gene trap in intron 4, thereby truncating NPHP5 at Leu87 and removing all known functional domains. At eye opening, Nphp5-/- mice exhibited absence of scotopic and photopic electroretinogram responses, a phenotype that resembles Leber congenital amaurosis. Outer segment transmembrane protein accumulation in Nphp5-/- endoplasmic reticulum was evident as early as postnatal day (P)6. EGFP-CETN2, a centrosome and transition zone marker, identified basal bodies in Nphp5-/- photoreceptors, but without fully developed transition zones. Ultrastructure of P6 and 10 Nphp5-/- photoreceptors revealed aberrant transition zones of reduced diameter. Nphp5-/- photoreceptor degeneration was complete at 1 mo of age but was delayed significantly in Nphp5-/-;Nrl-/- (cone only) retina. Nphp5-/- mouse embryonic fibroblast developed normal cilia, and Nphp5-/- kidney histology at 1 yr of age showed no significant pathology. Results establish that nephrocystin-5 is essential for photoreceptor outer segment formation but is dispensable for kidney and mouse embryonic fibroblast ciliary formation.-Ronquillo, C. C., Hanke-Gogokhia, C., Revelo, M. P., Frederick, J. M., Jiang, L., Baehr, W. Ciliopathy-associated IQCB1/NPHP5 protein is required for mouse photoreceptor outer segment formation. |
