Choroideremia is a rare, inherited disorder found almost exclusively in males and is characterized by progressive loss of vision due to degeneration of the choroid and retina. The disorder is caused by a mutation in the CHM gene on the X chromosome, which codes for an important protein called the Rab escort protein-1 (REP-1), which shuttles other cellular proteins towards the cell membrane to allow the passage of nutrients in and out of the cell. The absence of REP-1 results in nutrient deficiency and degeneration of light-sensitive photoreceptors embedded within the thin layer at the rear of the eye (the retinal pigment epithelium, RPE), and the choroid (a layer filled with blood vessels that nourish the retina).
In a study appearing online on January 12 in advance of print publication in the February 2006 issue of the Journal of Clinical Investigation, Miguel Seabra and colleagues from Imperial College London report the development of the first mouse model of this degenerative eye disease. The authors go on to demonstrate that choroideremia involves independently triggered degeneration of photoreceptors and the RPE, and that these events are caused by different trafficking defects in various subsets of defective Rab proteins. This is an important finding as it was previously believed that RPE degeneration resulted in photoreceptor degeneration, and vice-versa. Development of an animal model for this disease will allow researchers to assess potential therapies and gain a better understanding of disease mechanisms.
TITLE: Independent generation of photoreceptors and retinal pigment epithelium in conditional knockout mouse models of choroideremia
Brooke Grindlinger
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Journal of Clinical Investigation
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