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M.C. Seabra, T. Tolmachova, R. Anders, M. Abrink, J.S. Ramalho, C. Futter, F. Tonagel, N. Tanimoto, M. Seeliger, C. Huxley; Choroideremia Mouse Model Generated by Conditional Rep1 Knock–Out . Invest. Ophthalmol. Vis. Sci. 2005;46(13):3556.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: To create a mouse model of Choroideremia (CHM), avoiding the embryonic lethality associated with Rep1 deletion in mice. Methods: We used a conditional knock–out approach based on the Cre/loxP system of site–specific recombination. Initially, a mouse line carrying a Rep13loxP allele was produced and crossed with a transgenic line expressing tamoxifen–regulated MerCreMer transgene, which led to the generation of 3 Rep1 alleles: Rep1flox, Rep1null and Rep1null+Neo inherited by female offspring of tamoxifen–treated Rep13loxP/Y, Cre+ males. Results: Heterozygous null female carriers (Rep1 null/WT and Rep1null+Neo/WT) exhibit characteristic hallmarks of CHM: progressive degeneration of the photoreceptors and patchy depigmentation of the RPE. Similar to cells derived from CHM patients, Rab27a is found selectively underprenylated in tissues derived from these mice. Conclusions: These data demonstrate that Rep1 null/WT female carriers are a valid model of CHM, vital for future studies of disease progression and gene therapy trials.
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