Identification and functional analysis of the vision-specific BBS3 (ARL6) long isoform

Pamela R. Pretorius; Lisa M. Baye; Darryl Y. Nishimura; Charles C. Searby; Kevin Bugge; Baoli Yang; Robert F. Mullins; Edwin M. Stone; Val C. Sheffield; Diane C. Slusarski

doi:10.1371/journal.pgen.1000884

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Identification and functional analysis of the vision-specific BBS3 (ARL6) long isoform

Journal article

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Identification and functional analysis of the vision-specific BBS3 (ARL6) long isoform

Pamela R. Pretorius, Lisa M. Baye, Darryl Y. Nishimura, Charles C. Searby, Kevin Bugge, Baoli Yang, Robert F. Mullins, Edwin M. Stone, Val C. Sheffield and Diane C. Slusarski

PLoS genetics, Vol.6(3), pp.e1000884-e1000884

03/01/2010

DOI: 10.1371/journal.pgen.1000884

PMCID: PMC2841623

PMID: 20333246

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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.

Obstetrics and Gynecology

Details

Title: Subtitle: Identification and functional analysis of the vision-specific BBS3 (ARL6) long isoform
Creators: Pamela R. Pretorius
Lisa M. Baye
Darryl Y. Nishimura
Charles C. Searby
Kevin Bugge
Baoli Yang - University of Iowa
Robert F. Mullins
Edwin M. Stone
Val C. Sheffield
Diane C. Slusarski
Resource Type: Journal article
Publication Details: PLoS genetics, Vol.6(3), pp.e1000884-e1000884
DOI: 10.1371/journal.pgen.1000884
PMID: 20333246
PMCID: PMC2841623
NLM abbreviation: PLoS Genet
ISSN: 1553-7390
eISSN: 1553-7404
Publisher: United States
Grant note: R01EY110298 / NEI NIH HHS T32 HL007121 / NHLBI NIH HHS Howard Hughes Medical Institute R01 EY017168 / NEI NIH HHS R01EY017168 / NEI NIH HHS R01CA112369 / NCI NIH HHS R01 CA112369 / NCI NIH HHS
Language: English
Date published: 03/01/2010
Academic Unit: Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Medical Genetics and Genomics; Biology; BioVentures Center; Obstetrics and Gynecology; Ophthalmology and Visual Sciences
Record Identifier: 9983557772502771

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