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Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-10252

Brunner, S. Functional analysis of the Retinitis pigmentosa GTPase regulator(RPGR) gene. 2008, University of Zurich, Faculty of Medicine.



The retinitis pigmentosa GTPase regulator (RPGR) gene is mutated in several forms of photoreceptor degeneration resulting in severe visual impairment and probably blindness. Most patients develop Retinitis pigmentosa(RP), which is a clinically and genetically heterogeneous disease characterized by degeneration initially of rod and later in disease also of cone photoreceptors. Mutations in RPGR were also described in patients with cone-rod dystrophy, cone dystrophy, Coats’ like exsudative vitreoretinopathy and atrophic macular degeneration. Additionally, the spectrum of diseases due to RPGR mutations was further expanded by describing patients with a syndromic phenotype including RP, sinorespiratory infections and hearing problems and in patients manifesting with primary ciliary dyskinesia (PCD). To date, no phenotype-genotype correlation could be established. Evidence exist that genetic modifiers might act on disease expressivity as one mutation can lead to different phenotypes even within one family.
In order to gain a better understand the function of RPGR, two mouse models for RPGR-related diseases have been characterized in this study. The transgenic mouse line with Rpgr-overexpression of the wild type protein exhibits infertility. In contrast,the knock-in mouse model, harbouring a deletion of exon 4, develops either rod disease or cone-rod disease depending on the genetic background (BL/6 or BALB/c, respectively). The difference in retinal manifestations in the mouse resembles the clinical heterogeneity in humans. In addition, mislocalization of visual pigments was found to be an early pathologic event further mounting evidence that RPGR might be involved in the transport of proteins. Overall, the two mouse models further support the assumed function of RPGR in cilia and flagella. RPGR was for the first time shown to be involved in mouse flagellar biogenesis and can therefore be regarded as a novel candidate gene for male infertility. In addition, the knock-in mouse on the BALB/c background serves as a model for cone-dominated phenotypes including cone dystrophy, cone-rod dystrophy and even macular degeneration. The two knock-in lines provide a powerful tool to study the influence of modifier genes.


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Additional indexing

Item Type:Dissertation
Referees:Berger E, Berger W, Neuhauss S
Communities & Collections:04 Faculty of Medicine > Institute of Medical Molecular Genetics
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Deposited On:13 Jan 2009 16:13
Last Modified:05 Apr 2016 12:49
Number of Pages:167

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