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 Investigation2006, 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