title: Functional analysis of BBS3 A89V that results in non-syndromic retinal degeneration.
abstract: 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.
authors.affiliation: Department of Biology, Howard Hughes Medical Institute, University of Iowa, Iowa City, Iowa 52242, USA.
authors.forename: Pamela R
authors.initials: PR
authors.lastname: Pretorius
authors.forename: Mohammed A
authors.initials: MA
authors.lastname: Aldahmesh
authors.forename: Fowzan S
authors.initials: FS
authors.lastname: Alkuraya
authors.forename: Val C
authors.initials: VC
authors.lastname: Sheffield
authors.forename: Diane C
authors.initials: DC
authors.lastname: Slusarski
mesh_terms: D020727:ADP-Ribosylation Factors / Q000096:biosynthesis / Q000235:genetics*; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D020788:Bardet-Biedl Syndrome / Q000235:genetics*; D020868:Gene Silencing; D020460:Melanosomes / Q000378:metabolism; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000235:genetics*; D013216:Reflex, Startle; D012174:Retinitis Pigmentosa / Q000235:genetics*; D016415:Sequence Alignment; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics; D029961:Zebrafish Proteins / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D011994:Recombinant Proteins; D029961:Zebrafish Proteins; C491435:ARL6 protein, human; D020727:ADP-Ribosylation Factors; C548818:ARL6 protein, zebrafish