Functional characterization of retinitis pigmentosa causing RPGR mutations

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Retinitis pigmentosa (RP) is a progressive outer retinal dystrophy, affecting 1/3500 individuals in most populations. X-linked RP (XLRP) is one of the most severe forms of human retinal degeneration, as determined by age-of-onset and progression. Mutations in the retinitis pigmentosa GTPase regulator (RPGR) gene, responsible for the major subtype of XLRP, are the most common single cause of RP, accounting for 6-20% of all cases. We aim to investigate the functional role of RPGR mutations in the pathogenesis of XLRP.


Different RP-causing RPGR mutations were cloned into pCEP-4 expression vector and transfected into retinal pigment epithelium (RPE) 1 and IMCD3 cell lines. RPGR expression was detected by immunocytochemistry and western blotting. The pathological effects caused by RPGR mutations were characterized by immnocytochemistry.


The average length of cilia in RPE1 cells with over-expression of mutant RPGR are around 50-60% shorter compared to that in cells with over-expression of wild type RPGR. Cells with over-expression of RPGR mutant proteins exhibited stronger actin filaments. The frameshift RPGR mutations also cause aggregations in IMCD3 cell lines indicating that the mutant proteins are misfolded which may cause toxicity.


Mutant RPGR proteins have functional role in cilia defect through regulating actin remodelling,

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