Journal Article

Functional analysis of BBS3 A89V that results in non-syndromic retinal degeneration

Pamela R. Pretorius, Mohammed A. Aldahmesh, Fowzan S. Alkuraya, Val C. Sheffield and Diane C. Slusarski

in Human Molecular Genetics

Volume 20, issue 8, pages 1625-1632
Published in print April 2011 | ISSN: 0964-6906
Published online January 2011 | e-ISSN: 1460-2083 | DOI: http://dx.doi.org/10.1093/hmg/ddr039

Show Summary Details

Preview

Bardet–Biedl syndrome (BBS) is a syndromic form of retinal degeneration. Recently, homozygosity mapping with a consanguineous family with isolated retinitis pigmentosa identified a missense mutation in BBS3, a known BBS gene. The mutation in BBS3 encodes a single amino acid change at position 89 from alanine to valine. Since this amino acid is conserved in a wide range of vertebrates, we utilized the zebrafish model system to functionally characterize the BBS3 A89V mutation. Knockdown of bbs3 in zebrafish alters intracellular transport, a phenotype observed with knockdown of all BBS genes in the zebrafish, as well as visual impairment. Here, we find that BBS3 A89V is sufficient to rescue the transport delays induced by the loss of bbs3, indicating that this mutation does not affect the function of BBS3 as it relates to syndromic disease. BBS3L A89V, however, was unable to rescue vision impairment, highlighting a role for a specific amino acid within BBS3 that is necessary for visual function, but dispensable in other cell types. These data aid in our understanding of why patients with the BBS3 A89V missense mutation only present with isolated retinitis pigmentosa.

Journal Article.  3831 words.  Illustrated.

Subjects: Genetics and Genomics

Users without a subscription are not able to see the full content. Please, subscribe or login to access all content.