Résumé :
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Communication n° 524 Introduction : The dystrophin protein Dp71 is the major Duchenne muscular dystrophy (DMD) gene product in non-muscle tissues. In spite of the fact that Dp71 is required for the organization of dystrophin-associated protein complexes its precise function(s) remains unclear. Objectives : To determine in the mice visual system the phenotypes associated with the targeted inactivation of Dp71. Methods: Anatomical, electrophysiological, and histochemical analysis were performed on retina and lens from wild-type and Dp71 null-mice. Results : We established that the absence of Dp71 induced two "visual" phenotypes: i) a hypersensitivity of the retina to transient ischemia that results in a greater damage of ganglion cells; ii) a progressive perturbation in the lens leading to the apparition of a congenital cataract. The analysis of the molecular origin of these phenotypes lead us to discover that i) in retina, Dp71 was responsible of the localization and aggregation of two major proteins of the retinal homeostasis regulation: the potassium channel Kir4.1, and the water pore AQP4 in specific domains of Müller glial cells membrane; ii) in lens, Dp71 is deeply implicated in organizing and/or maintaining lens fibers probably by participating in a complex that involves beta-dystroglycan and AQP0. Conclusion : Our findings provide direct evidences for an essential role of Dp71 in visual system.
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