Abnormal photoresponses and light-induced apoptosis in rods lacking rhodopsin kinase

Proc Natl Acad Sci U S A. 1999 Mar 30;96(7):3718-22. doi: 10.1073/pnas.96.7.3718.

Abstract

Phosphorylation is thought to be an essential first step in the prompt deactivation of photoexcited rhodopsin. In vitro, the phosphorylation can be catalyzed either by rhodopsin kinase (RK) or by protein kinase C (PKC). To investigate the specific role of RK, we inactivated both alleles of the RK gene in mice. This eliminated the light-dependent phosphorylation of rhodopsin and caused the single-photon response to become larger and longer lasting than normal. These results demonstrate that RK is required for normal rhodopsin deactivation. When the photon responses of RK-/- rods did finally turn off, they did so abruptly and stochastically, revealing a first-order backup mechanism for rhodopsin deactivation. The rod outer segments of RK-/- mice raised in 12-hr cyclic illumination were 50% shorter than those of normal (RK+/+) rods or rods from RK-/- mice raised in constant darkness. One day of constant light caused the rods in the RK-/- mouse retina to undergo apoptotic degeneration. Mice lacking RK provide a valuable model for the study of Oguchi disease, a human RK deficiency that causes congenital stationary night blindness.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Crosses, Genetic
  • Darkness
  • Eye Proteins*
  • G-Protein-Coupled Receptor Kinase 1
  • Homozygote
  • Humans
  • Light
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Phosphorylation
  • Photic Stimulation
  • Photoperiod
  • Protein Kinase C / metabolism
  • Protein Kinases / deficiency
  • Protein Kinases / genetics
  • Protein Kinases / metabolism*
  • Restriction Mapping
  • Retinal Rod Photoreceptor Cells / cytology
  • Retinal Rod Photoreceptor Cells / physiology*
  • Retinal Rod Photoreceptor Cells / radiation effects
  • Rhodopsin / metabolism
  • Rod Cell Outer Segment / cytology
  • Rod Cell Outer Segment / physiology
  • Rod Cell Outer Segment / radiation effects

Substances

  • Eye Proteins
  • Rhodopsin
  • Protein Kinases
  • Protein Kinase C
  • G-Protein-Coupled Receptor Kinase 1
  • GRK1 protein, human
  • Grk1 protein, mouse

Associated data

  • GENBANK/AF085240