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Autosomal recessive retinitis pigmentosa E150K opsin mice exhibit photoreceptor disorganization.

The pathophysiology of the E150K mutation in the rod opsin gene associated with autosomal recessive retinitis pigmentosa (arRP) has yet to be determined. We generated knock-in mice carrying a single nucleotide change in exon 2 of the rod opsin gene resulting in the E150K mutation. This novel mouse model displayed severe retinal degeneration affecting rhodopsin's stabilization of rod outer segments (ROS). Homozygous E150K (KK) mice exhibited early-onset retinal degeneration, with disorganized ROS structures, autofluorescent deposits in the subretinal space, and aberrant photoreceptor phagocytosis. Heterozygous (EK) mice displayed a delayed-onset milder retinal degeneration. Further, mutant receptors were mislocalized to the inner segments and perinuclear region. Though KK mouse rods displayed markedly decreased phototransduction, biochemical studies of the mutant rhodopsin revealed only minimally affected chromophore binding and G protein activation. Ablation of the chromophore by crossing KK mice with mice lacking the critical visual cycle protein LRAT slowed retinal degeneration, whereas blocking phototransduction by crossing KK mice with GNAT1-deficient mice slightly accelerated this process. This study highlights the importance of proper higher-order organization of rhodopsin in the native tissue and provides information about the signaling properties of this mutant rhodopsin. Additionally, these results suggest that patients heterozygous for the E150K mutation should be periodically reevaluated for delayed-onset retinal degeneration.

Pubmed ID: 23221340


  • Zhang N
  • Kolesnikov AV
  • Jastrzebska B
  • Mustafi D
  • Sawada O
  • Maeda T
  • Genoud C
  • Engel A
  • Kefalov VJ
  • Palczewski K


The Journal of clinical investigation

Publication Data

January 2, 2013

Associated Grants

  • Agency: NEI NIH HHS, Id: EY 021126
  • Agency: NEI NIH HHS, Id: EY002687
  • Agency: NEI NIH HHS, Id: EY009339
  • Agency: NEI NIH HHS, Id: EY019312
  • Agency: NEI NIH HHS, Id: K08EY0190
  • Agency: NEI NIH HHS, Id: K08EY019880
  • Agency: NEI NIH HHS, Id: P30 EY11373
  • Agency: NEI NIH HHS, Id: R24 EY021126
  • Agency: NIGMS NIH HHS, Id: T32 GM007250
  • Agency: NEI NIH HHS, Id: T32EY007157
  • Agency: NIGMS NIH HHS, Id: T32GM007250

Mesh Terms

  • Amino Acid Substitution
  • Animals
  • Exons
  • GTP-Binding Protein alpha Subunits
  • Humans
  • Mice
  • Mice, Mutant Strains
  • Mutation, Missense
  • Phagocytosis
  • Protein Transport
  • Retinal Rod Photoreceptor Cells
  • Retinitis Pigmentosa
  • Rhodopsin
  • Transducin