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
-
- Mice, Mutant Strains
- Mice
- RNA, Messenger/genetics
- RNA, Messenger/metabolism
- Organ Specificity/drug effects
- Reflex, Startle/drug effects
- Protein Transport/drug effects
- Molecular Sequence Data
- Amino Acid Sequence
- Animals
- Vision, Ocular*/drug effects
- Protein Isoforms/chemistry
- Protein Isoforms/genetics
- Protein Isoforms/metabolism
- Gene Knockdown Techniques
- Phenotype
- Zebrafish Proteins/chemistry
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism*
- Eye Abnormalities/complications
- Eye Abnormalities/pathology
- Eye Abnormalities/physiopathology
- Photoreceptor Cells, Vertebrate/drug effects
- Photoreceptor Cells, Vertebrate/metabolism
- Photoreceptor Cells, Vertebrate/pathology
- Ganglia/drug effects
- Ganglia/metabolism
- Ganglia/pathology
- Humans
- Zebrafish
- ADP-Ribosylation Factors/chemistry
- ADP-Ribosylation Factors/deficiency
- ADP-Ribosylation Factors/genetics
- ADP-Ribosylation Factors/metabolism*
- Bardet-Biedl Syndrome/complications
- Bardet-Biedl Syndrome/genetics
- Bardet-Biedl Syndrome/pathology
- Bardet-Biedl Syndrome/physiopathology
- Oligonucleotides, Antisense/pharmacology
- Gene Expression Regulation/drug effects
- Rod Opsins/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