Defective development of photoreceptor membranes in a mouse model of recessive retinal degeneration

Document Type

Article

Abstract

Retinal neurodegeneration occurs in several inherited diseases. Some of the most severe disease alleles involve mutations at the C-terminus of rhodopsin, but in no case is the pathogenic mechanism leading to cell death well understood. We have examined a mouse model of recessive retinal degeneration caused by a knock-in of a human rhodopsin-EGFP fusion gene (hrhoG/hrhoG) at the rhodopsin locus. Whereas heterozygous mutant mice were indistinguishable from control mice, homozygous mutant mice had retinal degeneration. We hypothesized that degeneration might be due to aberrant rhodopsin signaling; however, inhibiting signaling by rearing mice in total darkness had no effect on the rate of degeneration. Using confocal and electron microscopy, we identified the fundamental defect as failed biogenesis of disk membranes, which is observed at the earliest stages of outer segment development. These results reveal that in addition to its role in transport and sorting of rhodopsin to disk membranes, rhodopsin is also essential for formation of disks.

Medical Subject Headings

Animals; Cell Membrane (metabolism, pathology, ultrastructure); Dark Adaptation (physiology); Electroretinography; Green Fluorescent Proteins (genetics); Mice; Mice, Transgenic; Microscopy, Electron, Transmission; Models, Animal; Retinal Degeneration (genetics, metabolism, pathology); Retinal Rod Photoreceptor Cells (metabolism, pathology, ultrastructure); Rhodopsin (genetics, physiology, ultrastructure); Rod Cell Outer Segment (ultrastructure); Vision, Ocular

Publication Date

12-1-2006

Publication Title

Vision research

ISSN

0042-6989

Volume

46

Issue

27

First Page

4510

Last Page

8

PubMed ID

16979686

Digital Object Identifier (DOI)

10.1016/j.visres.2006.07.012

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