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Research article - Peer-reviewed, 2006

Independent degeneration of photoreceptors and retinal pigment epithelium in conditional knockout mouse models of choroideremia

Tolmachova, Tanya; Åbrink, Magnus; Seabra, Miguel C.

Abstract

Choroideremia (CHM) is an X-linked degeneration of the retinal pigment epithelium (RPE), photoreceptors, and choroid, caused by loss of function of the CHM/REP1 gene. REP1 is involved in lipid modification (prenylation) of Rab GTPases, key regulators of intracellular vesicular transport and organelle dynamics. To study the pathogenesis of CHM and to develop a model for assessing gene therapy, we have created a conditional mouse knockout of the Chm gene. Heterozygous-null females exhibit characteristic hallmarks of CHM: progressive degeneration of the photoreceptors, patchy depigmentation of the RPE, and Rab prenylation defects. Using tamoxifen-inducible and tissue-specific Cre expression in combination with floxed Chm alleles, we show that CHM pathogenesis involves independently triggered degeneration of photoreceptors and the RPE, associated with different subsets of defective Rabs.

Published in

Journal of Clinical Investigation
2006, volume: 116, number: 2, pages: 386-394
Publisher: AMER SOC CLINICAL INVESTIGATION INC

Authors' information

Tolmachova, Tanya
Imperial College London
Swedish University of Agricultural Sciences, Department of Molecular Biosciences
Seabra, Miguel C.
Imperial College London

UKÄ Subject classification

Cell and Molecular Biology

Publication Identifiers

DOI: https://doi.org/10.1172/JCI26617

URI (permanent link to this page)

https://res.slu.se/id/publ/41345