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M.M. Abd–El–Barr, E.R. Eichers, O.M. Shoukfeh, Z. Yang, J. Zhang, R.A. Lewis, J.R. Lupski, S.M. Wu; Cone–Rod Dystrophy, Mislocalization of Visual Pigments, and Inner Retinal Changes in a Mouse Model of Bardet–Biedl Syndrome . Invest. Ophthalmol. Vis. Sci. 2006;47(13):2971.
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Bardet–Biedl syndrome (BBS) is a rare oligogenic disorder exhibiting both clinical and genetic heterogeneity. The syndrome is characterized by mental retardation, post–axial polydactylia, obesity, hypogenitalism, renal abnormalities, retinal dystrophy, and several less obvious features. In this study, we characterize further the retinal phenotype of Bbs4–null mice to understand the pathophysiology of Bardet–Biedl syndrome.
We used immunohistochemistry and electroretinography for structural and functional analyses.
1) Cone–rod dystrophy. As early as 4 weeks of age, Bbs4–null mice showed severe deterioration of both rod and cone systems. Rod photoreceptor function as evidenced by a–wave analysis demonstrated that Bbs4–null animals had a significantly smaller amax compared to wild type (26% of wild–type value, p < 0.001). Cone dysfunction was more severe; at 4 weeks of age the null mice had 12% of wild–type cone b–wave function (p < 0.001). This cone–rod dystrophy was progressive, with a further decrease in all parameters at 14 weeks of age. Anatomically, hematoxylin and eosin staining of the retina demonstrated progressive deterioration of the outer nuclear layer (ONL). 2) Misolocalization of visual pigments. Both cone and rod visual pigments accumulated in the inner segments and cell bodies of the photoreceptors in the Bbs4–null mice, consistent with compromised intra–flagellar transport. 3) Inner retinal changes. Increased scotopic b– to a–wave ratio (p < 0.001) and increased time to peak of the scotopic rod B wave (p < 0.01) were suggestive of functional inner retinal changes. There was also a loss of normal cone pedicle structure.
Bbs4–null mice exhibit a cone–rod dystrophy, problems with intra–flagellar transport, and evidence of inner retinal changes. These mice seem to recapitulate human disease, and offer an unique opportunity to further understand the pathophysiology of this disorder and other retinal cone–rod dystrophies.
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