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K. Chekroud, M. O. Pequignot, L. Guillou, E. Brun, C. P. Hamel, P. Brabet; Exploration of the Visual Cycle in Fatp1-Deficient Mice. Invest. Ophthalmol. Vis. Sci. 2010;51(13):1301.
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In the visual cycle, the limiting step is the isomerisation of all-trans to 11-cis retinoids through the RPE-specific isomerohydrolase RPE65. We previously showed that FATP1 (fatty acid transport protein 1) interacts physically with RPE65, and that FATP1 overexpression inhibits 11-cis retinal production in Sf9 and HEK cells. Here we evaluated the effect of the lack of this protein in a fatp1-/- mouse model.
Neuroretina and RPE morphology and function were studied by optic and electron microscopy, and electroretinography, respectively. Retinoids were separated and quantified through reverse phase HPLC and lipofuscin was measured by spectrophotometry. Using Q-PCR, we quantified the transcripts of the members of FATP family as well as those of the visual cycle components: RPE65 and rhodopsin.
1.No fatp1 transcipts were detected in retina and RPE of fatp1-/- mice by Q-PCR.2.No differences were found between fatp1-/- and fatp1+/+ mice, in either 2 month- or 20 to 24 month-old animals. There was no change in retinal morphology, ERG responses, retinal lipofuscin content and kinetics of chromophore regeneration.3.However, mRNA quantification revealed variations between the two genotypes. We found that fatp1-/- mice retina contained a 2-fold decrease in rhodopsin and RPE showed an 8-fold increase in RPE65 transcripts compared to fatp1+/+ animals. We also observed that FATP4 mRNA was 4-fold increased while FATP6 mRNA was decreased by 2-fold in RPE.
The lack of FATP1 has no effect on visual function and mice do not undergo retinal degeneration. This could suggest that FATP1 may not be an essential component of the visual cycle or that its lack is partly compensated by FATP4 increase.Moreover, the dysregulation of RPE65 and rhodopsin mRNA shows that FATP1 could play a role in the transcription regulation of the visual cycle partners. Quantification of the protein components and the nature of this regulation are currently under investigation.
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