Abstract
Bardet-Biedl Syndrome (BBS) is a heterogeneous syndromic form of retinal degeneration. We have identified a novel transcript of a known BBS gene, BBS3 (ARL6), which includes an additional exon. This transcript, BBS3L, is evolutionally conserved and is expressed predominantly in the eye, suggesting a specialized role in vision. Using antisense oligonucleotide knockdown in zebrafish, we previously demonstrated that bbs3 knockdown results in the cardinal features of BBS in zebrafish, including defects to the ciliated Kupffer's Vesicle and delayed retrograde melanosome transport. Unlike bbs3, knockdown of bbs3L does not result in Kupffer's Vesicle or melanosome transport defects, rather its knockdown leads to impaired visual function and mislocalization of the photopigment green cone opsin. Moreover, BBS3L RNA, but not BBS3 RNA, is sufficient to rescue both the vision defect as well as green opsin localization in the zebrafish retina. In order to demonstrate a role for Bbs3L function in the mammalian eye, we generated a Bbs3L-null mouse that presents with disruption of the normal photoreceptor architecture. Bbs3L-null mice lack key features of previously published Bbs-null mice, including obesity. These data demonstrate that the BBS3L transcript is required for proper retinal function and organization.
Highlights
Visual impairment and blindness have far reaching implications for society
Retinitis pigmentosa (RP), a disorder of retinal degeneration resulting in blindness, occurs due to mutations in dozens of different genes encoding proteins with highly diverse functions
We have studied a syndromic form of RP known as BardetBiedl Syndrome (BBS), which leads to degeneration of the photoreceptor cells and is associated with non-vision abnormalities including obesity, hypertension, diabetes, and congenital abnormalities of the kidney, heart, and limbs
Summary
But collectively common Mendelian disorders can cause blindness. One of these disorders is a heterogeneous syndromic form of retinal degeneration, BardetBiedl Syndrome (BBS, OMIM 209900). This pleiotropic disorder is characterized by retinal degeneration, obesity, polydactyly, renal abnormalities, hypogenitalism and cognitive impairment [1,2,3,4]. There is variability in the ocular phenotype between individuals, BBS patients typically present with early and progressive photoreceptor degeneration, leading to both central and peripheral vision loss by the third decade of life [1,6,7,8,9,10,11,12,13]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
