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

Pamela R Pretorius; Mohammed A Aldahmesh; Fowzan S Alkuraya; Val C Sheffield; Diane C Slusarski

doi:10.1093/hmg/ddr039

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

Journal article

Open access

Peer reviewed

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

Human molecular genetics, Vol.20(8), pp.1625-1632

04/15/2011

DOI: 10.1093/hmg/ddr039

PMCID: PMC3063988

PMID: 21282186

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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.

Amino Acid Sequence

Zebrafish Proteins - biosynthesis

Gene Silencing

Molecular Sequence Data

Retinitis Pigmentosa - genetics

Recombinant Proteins - genetics

Mutation, Missense

Recombinant Proteins - biosynthesis

Zebrafish - embryology

Zebrafish - genetics

Amino Acid Motifs

Sequence Alignment

Animals

ADP-Ribosylation Factors - biosynthesis

Reflex, Startle

Bardet-Biedl Syndrome - genetics

Zebrafish Proteins - genetics

ADP-Ribosylation Factors - genetics

Melanosomes - metabolism

Details

Title: Subtitle: Functional analysis of BBS3 A89V that results in non-syndromic retinal degeneration
Creators: Pamela R Pretorius - Department of Biology, Howard Hughes Medical Institute, University of Iowa, Iowa City, Iowa 52242, USA
Mohammed A Aldahmesh
Fowzan S Alkuraya
Val C Sheffield
Diane C Slusarski
Resource Type: Journal article
Publication Details: Human molecular genetics, Vol.20(8), pp.1625-1632
DOI: 10.1093/hmg/ddr039
PMID: 21282186
PMCID: PMC3063988
NLM abbreviation: Hum Mol Genet
ISSN: 0964-6906
eISSN: 1460-2083
Publisher: England
Grant note: REY110298 / PHS HHS R01 EY011298 / NEI NIH HHS R01CA112369 / NCI NIH HHS Howard Hughes Medical Institute REY017168 / PHS HHS
Language: English
Date published: 04/15/2011
Academic Unit: Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Medical Genetics and Genomics; Biology; Ophthalmology and Visual Sciences
Record Identifier: 9983992061602771

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