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
  • RNA, Messenger/genetics
  • RNA, Messenger/metabolism
  • Phenotype
  • Mice, Mutant Strains
  • Oligonucleotides, Antisense/pharmacology
  • Gene Knockdown Techniques
  • ADP-Ribosylation Factors/chemistry
  • ADP-Ribosylation Factors/deficiency
  • ADP-Ribosylation Factors/genetics
  • ADP-Ribosylation Factors/metabolism*
  • Amino Acid Sequence
  • Gene Expression Regulation/drug effects
  • Molecular Sequence Data
  • Vision, Ocular*/drug effects
  • Photoreceptor Cells, Vertebrate/drug effects
  • Photoreceptor Cells, Vertebrate/metabolism
  • Photoreceptor Cells, Vertebrate/pathology
  • Rod Opsins/metabolism
  • Zebrafish
  • Protein Transport/drug effects
  • Mice
  • Zebrafish Proteins/chemistry
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
  • Protein Isoforms/chemistry
  • Protein Isoforms/genetics
  • Protein Isoforms/metabolism
  • Eye Abnormalities/complications
  • Eye Abnormalities/pathology
  • Eye Abnormalities/physiopathology
  • Bardet-Biedl Syndrome/complications
  • Bardet-Biedl Syndrome/genetics
  • Bardet-Biedl Syndrome/pathology
  • Bardet-Biedl Syndrome/physiopathology
  • Humans
  • Reflex, Startle/drug effects
  • Animals
  • Ganglia/drug effects
  • Ganglia/metabolism
  • Ganglia/pathology
  • Organ Specificity/drug effects
(all 41)
PubMed
20333246 Full text @ PLoS Genet.
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
Figures
Figure Gallery (4 images)
Show all Figures
Expression
Phenotype
Mutations / Transgenics
No data available
Human Disease / Model
Human Disease Fish Conditions Evidence
retinitis pigmentosaTAS
1 - 1 of 1
Show
Sequence Targeting Reagents
Target Reagent Reagent Type
arl6MO1-arl6MRPHLNO
arl6MO3-arl6MRPHLNO
crxMO3-crxMRPHLNO
1 - 3 of 3
Show
Fish
Antibodies
No data available
Orthology
No data available
Engineered Foreign Genes
No data available
Mapping
No data available