ATRX is a SWI/SNF-like chromatin remodeling protein mutated in several X-linked mental retardation syndromes. In addition to severe mental retardation, athalassemia and urogenital abnormalities, several vision defects are present in patients, although these have been greatly under reported. Upon closer examination, visual defects were noted in 23% of patients, with optic atrophy, pale disc and refractive errors being the most commonly reported abnormalities. We report here that Atrx is

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... y expressed in the neuroprogenitor pool during retinal differentiation as well as in all cell types of the mature retina with the exception of rod photoreceptors. To further investigate the impact of ATRX ablation on vision, we used a conditional gene-targeting approach to generate transgenic mice in which inactivation of Atrx occurs under the control of the retina specific element of murine Pax6. Our results show that inactivation of Atrx results in a ∼25-30% reduction in amacrine and horizontal interneurons. The loss of amacrine and horizontal cells resulted from increased cell death in a period which corresponds with a change in Atrx nuclear localization and retinal synaptogenesis in these cell types. Furthermore, our work illustrates that Atrx inactivation is associated with attenuated b-wave amplitude as measured by ERG analysis. Based on these findings it seems that ATRX may play a critical role in the mediation of retinal synaptogenesis and that increased cell loss may contribute to the visual defect observed in ATRX patients.