TY  - JOUR
A1  - Ronquillo, Cecinio C.
A1  - Hanke-Gogokhia, Christin
A1  - Revelo, Monica P.
A1  - Frederick, Jeanne M.
A1  - Jiang, Li
A1  - Baehr, Wolfgang
T1  - Ciliopathy-associated IQCB1/NPHP5 protein is required for mouse photoreceptor outer segment formation
JF  - The FASEB journal : the official journal of the Federation of American Societies for Experimental Biology
N2  - 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 -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.
KW  - Senior-LOken syndrome
KW  - nephronophthisis
KW  - Leber congenital amaurosis
KW  - nephrocystins
Y1  - 2016
U6  - https://doi.org/10.1096/fj.201600511R
SN  - 0892-6638
SN  - 1530-6860
VL  - 30
SP  - 3400
EP  - 3412
PB  - Federation of American Societies for Experimental Biology
CY  - Bethesda
ER  -