Rhodopsin kinase (RK), a rod photoreceptor cytosolic
enzyme, plays a key role in the normal deactivation and recovery of the photoreceptor after exposure to light. To date, three different mutations in the RK locus have been associated with
Oguchi disease, an autosomal recessive form of stationary
night blindness in man characterized in part by delayed photoreceptor recovery [Yamamoto, S. , Sippel, K. C., Berson, E. L. & Dryja, T. P. (1997)
Nat. Genet. 15, 175-178]. Two of the mutations involve exon 5, and the remaining mutation occurs in exon 7. Known exon 5 mutations include the deletion of the entire exon sequence [HRK(X5 del)] and a missense change leading to a Val380Asp substitution in the encoded product (HRKV380D). The mutation in exon 7 is a 4-bp deletion in
codon 536 leading to premature termination of the encoded
polypeptide [HRKS536(4-bp del)]. To provide biochemical evidence for pathogenicity of these mutations, wild-type human
rhodopsin kinase (HRK) and mutant forms HRKV380D and HRKS536(4-bp del) were expressed in COS7 cells and their activities were compared. Wild-type HRK catalyzed light-dependent phosphorylation of
rhodopsin efficiently. In contrast, both
mutant proteins were markedly deficient in catalytic activity with HRKV380D showing virtually no detectible activity and HRKS536(4-bp del) only minimal light-dependent activity. These results provide biochemical evidence to support the pathogenicity of the RK mutations in man.