Purchase this article with an account.
X. Shu, Z. Zeng, P. Gautier, A. Lennon, M. Gakovic, E. Patton, A. Wright; RPGR Deficiency Results in Retinal Degeneration in Zebrafish. Invest. Ophthalmol. Vis. Sci. 2010;51(13):4047.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
X-linked retinitis pigmentosa (XLRP) is one of the most severe forms of human retinal degeneration, as determined by age-of-onset and progression, and accounts for 6-20% of all RP cases. The RP GTPase Regulator (RPGR) gene is mutated in 70-80% of XLRP patients. Over 290 mutations in RPGR have been identified, which can give rise to central or peripheral retinal dystrophies. The function of RPGR is unclear although the N-terminal half of RPGR (exons 2-11) is structurally similar to the regulator of chromosome condensation (RCC1). Here we use zebrafish as a model to investigate RPGR function.
Zebrafish RPGR orthologues were predicted by bioinformatic analysis and confirmed by reverse transcriptase polymerase chain reaction (RT-PCR). Zebrafish RPGR expression patterns during development and in adult tissues were examined by RT-PCR and whole-mount in situ hybridisation, while the localisation was studied by immunostaining. Knock-down of zebrafish RPGR was carried out by morpholino injections. The phenotype of the RPGR deficient morphants was analysed using standardized procedures.
We identified and examined the expression of zebrafish RPGR. We generated a vertebrate model of RPGR insufficiency using antisense methodology in zebrafish, which showedabnormal retinal development andretinal degeneration due to extensive apoptosis. Human RPGRORF15 can rescue the zebrafish RPGR-deficient phenotype.
This PDF is available to Subscribers Only