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Tanya Lee Dilan, Thamaraiselvi Saravanan, Visvanathan Ramamurthy; Bardet-Biedl syndrome-8 (Bbs8) is critical for mouse cone photoreceptor function and viability. Invest. Ophthalmol. Vis. Sci. 2016;57(12):189.
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© 2017 Association for Research in Vision and Ophthalmology.
Bardet-Biedl syndrome (BBS) is an autosomal recessive ciliopathy characterized by several abnormalities including vision loss in humans. To date, 19 genes have been identified to cause BBS. Several of these BBS proteins form a stable octameric complex termed the BBSome, which is thought to be involved in ciliogenesis and/or protein trafficking. BBS8, a tetratricopeptide repeat protein, is part of this core BBSome complex. Mutations in Bbs8 have been reported to cause non-syndromic retinitis pigmentosa, yet little is known about the function of BBS8 in photoreceptor cells. In this study, we sought to determine the importance of BBS8 in protein trafficking and cilia formation in cone photoreceptor cells.
Bbs8 was conditionally knocked out in cone photoreceptors of mice using the Cre-loxP approach. Visual responses of photoreceptors were assessed by electroretinography. The retinal morphology was examined by light- and electron microscopy. Protein expression and subcellular localization were analyzed by Western blotting and immunofluorescence microscopy, respectively. All conditional mutants were compared to their littermate controls (n=4).
Cones lacking BBS8 exhibited severe loss of visual function soon after mice reached four months of age, while being mostly unaffected in younger mice. Rod photoresponses remained unaltered at all ages. In agreement with our functional analyses, retinal sections stained with PNA show markedly reduced cone density. Immunohistochemical staining of retinal sections with multiple cone protein markers in Bbs8 conditional mice were also significantly reduced at four months of age.
Our results show that BBS8 is essential for cone photoreceptor function and survival. We are currently exploring the mechanistic basis of cone photoreceptor cell pathology associated with loss of BBS8.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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