PUBLICATION
Identification and functional analysis of the vision-specific BBS3 (ARL6) long isoform
- Authors
- Pretorius, P.R., Baye, L.M., Nishimura, D.Y., Searby, C.C., Bugge, K., Yang, B., Mullins, R.F., Stone, E.M., Sheffield, V.C., and Slusarski, D.C.
- ID
- ZDB-PUB-100330-16
- Date
- 2010
- Source
- PLoS Genetics 6(3): e1000884 (Journal)
- Registered Authors
- Baye, Lisa, Slusarski, Diane C.
- Keywords
- Zebrafish, Embryos, Retina, Photoreceptors, Mouse models, Eyes, Vision, RNA transport
- MeSH Terms
-
- ADP-Ribosylation Factors/chemistry
- ADP-Ribosylation Factors/deficiency
- ADP-Ribosylation Factors/genetics
- ADP-Ribosylation Factors/metabolism*
- Amino Acid Sequence
- Animals
- Bardet-Biedl Syndrome/complications
- Bardet-Biedl Syndrome/genetics
- Bardet-Biedl Syndrome/pathology
- Bardet-Biedl Syndrome/physiopathology
- Eye Abnormalities/complications
- Eye Abnormalities/pathology
- Eye Abnormalities/physiopathology
- Ganglia/drug effects
- Ganglia/metabolism
- Ganglia/pathology
- Gene Expression Regulation/drug effects
- Gene Knockdown Techniques
- Humans
- Mice
- Mice, Mutant Strains
- Molecular Sequence Data
- Oligonucleotides, Antisense/pharmacology
- Organ Specificity/drug effects
- Phenotype
- Photoreceptor Cells, Vertebrate/drug effects
- Photoreceptor Cells, Vertebrate/metabolism
- Photoreceptor Cells, Vertebrate/pathology
- Protein Isoforms/chemistry
- Protein Isoforms/genetics
- Protein Isoforms/metabolism
- Protein Transport/drug effects
- RNA, Messenger/genetics
- RNA, Messenger/metabolism
- Reflex, Startle/drug effects
- Rod Opsins/metabolism
- Vision, Ocular*/drug effects
- Zebrafish
- Zebrafish Proteins/chemistry
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism*
- PubMed
- 20333246 Full text @ PLoS Genet.
Citation
Pretorius, P.R., Baye, L.M., Nishimura, D.Y., Searby, C.C., Bugge, K., Yang, B., Mullins, R.F., Stone, E.M., Sheffield, V.C., and Slusarski, D.C. (2010) Identification and functional analysis of the vision-specific BBS3 (ARL6) long isoform. PLoS Genetics. 6(3):e1000884.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping