RGD Reference Report - Spontaneous activity of opsin apoprotein is a cause of Leber congenital amaurosis. - Rat Genome Database

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Spontaneous activity of opsin apoprotein is a cause of Leber congenital amaurosis.

Authors: Woodruff, ML  Wang, Z  Chung, HY  Redmond, TM  Fain, GL  Lem, J 
Citation: Woodruff ML, etal., Nat Genet 2003 Oct;35(2):158-64. Epub 2003 Sep 21.
RGD ID: 737730
Pubmed: PMID:14517541   (View Abstract at PubMed)
DOI: DOI:10.1038/ng1246   (Journal Full-text)

Mutations in Rpe65 disrupt synthesis of the opsin chromophore ligand 11-cis-retinal and cause Leber congenital amaurosis (LCA), a severe, early-onset retinal dystrophy. To test whether light-independent signaling by unliganded opsin causes the degeneration, we used Rpe65-null mice, a model of LCA. Dark-adapted Rpe65-/- mice behaved as if light adapted, exhibiting reduced circulating current, accelerated response turn-off, and diminished intracellular calcium. A genetic block of transducin signaling completely rescued degeneration irrespective of an elevated level of retinyl ester. These studies clearly show that activation of sensory transduction by unliganded opsin, and not the accumulation of retinyl esters, causes light-independent retinal degeneration in LCA. A similar mechanism may also be responsible for degeneration induced by vitamin A deprivation.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Leber congenital amaurosis 2  ISORpe65 (Mus musculus)737730; 737730 RGD 
Leber congenital amaurosis 2  IMP 737730 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Rpe65  (retinoid isomerohydrolase RPE65)

Genes (Mus musculus)
Rpe65  (retinal pigment epithelium 65)

Genes (Homo sapiens)
RPE65  (retinoid isomerohydrolase RPE65)

Objects referenced in this article
Gene Cyp7a1 cytochrome P450, family 7, subfamily a, polypeptide 1 Mus musculus
Gene Gnat1 G protein subunit alpha transducin 1 Mus musculus

Additional Information