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D. Hong, R. Wright; Overexpression of RPGR Default Variant Leads to Retinal Degeneration. Invest. Ophthalmol. Vis. Sci. 2008;49(13):2201.
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© ARVO (1962-2015); The Authors (2016-present)
The retinitis pigmentosa GTPase regulator (RPGR) is essential for viability of photoreceptors and is expressed as default and ORF15 variants due to alternative splicing. Both variants are expressed at similar levels in adult retina. This study was designed to examine the role of RPGR default variant in photoreceptor development and survival.
A mouse RPGR default cDNA was placed under the control of chicken beta-actin (CBA) hybrid promoter and was introduced to C57/BL6 fertilized eggs by pronuclear injection. Founder mice were crossed with C57/BL6 wild type and RPGR knockout mice. Retinal phenotype of transgenic mice was analyzed by histology and immunocytochemistry.
Multiple lines of transgenic mice were identified and analyzed. One line expressed several fold higher level of default RPGR variant in the retina. The transgenic mice showed normal retinal development but exhibited severe photoreceptor degeneration at a rate faster than that of RPGR KO mice. No apparent phenotypic differences between RPGR KO and WT background were observed. Immunohistochemical analyses of retinal sections from P20 and 1.5 month old transgenic mice revealed mislocalized cone opsins and upregulated GFAP.
Overexpression of the RPGR default variant in the retina does not affect photoreceptor development, but does lead to photoreceptor degeneration. Our findings suggest that each RPGR variants possesses distinct function and strict control of their expression may be required for normal function.
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