Bardet-Biedl syndrome genes are important in retrograde intracellular trafficking and Kupffer's vesicle cilia function

Hsan-Jan Yen; Marwan K Tayeh; Robert F Mullins; Edwin M Stone; Val C Sheffield; Diane C Slusarski

doi:10.1093/hmg/ddi468

Back

Bardet-Biedl syndrome genes are important in retrograde intracellular trafficking and Kupffer's vesicle cilia function

Journal article

Open access

Peer reviewed

Bardet-Biedl syndrome genes are important in retrograde intracellular trafficking and Kupffer's vesicle cilia function

Hsan-Jan Yen, Marwan K Tayeh, Robert F Mullins, Edwin M Stone, Val C Sheffield and Diane C Slusarski

Human molecular genetics, Vol.15(5), pp.667-677

03/01/2006

DOI: 10.1093/hmg/ddi468

PMID: 16399798

Files and links (1)

url

https://doi.org/10.1093/hmg/ddi468View

Published (Version of record) Open Access

Abstract

Bardet-Biedl syndrome (BBS) is characterized by obesity, retinopathy, polydactyly, cognitive impairment, renal and cardiac anomalies as well as hypertension and diabetes. The nine known BBS genes do not appear to belong to the same functional category; yet mutation of these genes results in a nearly identical pleiotropic phenotype. Although the precise functions of the BBS proteins have yet to be determined, current data support a role in cilia function and intraflagellar transport. To gain insight into the biological processes controlled by BBS genes, we embarked on studies of six BBS orthologues from zebrafish. Knockdown of zebrafish bbs2, bbs4, bbs5, bbs6, bbs7 or bbs8 results in disruption of Kupffer's vesicle (KV), a ciliated organ thought to play a role in left-right patterning. KV defects are due to a progressive loss of cilia within the vesicle and result in subsequent alterations to organ laterality. We also note a specific defect altering retrograde melanosome transport. These studies are the first to comprehensively compare the diverse group of BBS genes in parallel and demonstrate a common role in intracellular trafficking, indicating that BBS proteins are involved in general organelle trafficking.

Immunohistochemistry

Humans

Zebrafish - embryology

Eye - embryology

Gene Expression Regulation, Developmental

Body Patterning

Cloning, Molecular

Caffeine - pharmacology

Bardet-Biedl Syndrome - genetics

Fluorescent Antibody Technique, Indirect

Melanosomes - drug effects

Oligonucleotides, Antisense - pharmacology

Eye - ultrastructure

Zebrafish Proteins - chemistry

Animals, Genetically Modified

Zebrafish Proteins - metabolism

Reverse Transcriptase Polymerase Chain Reaction

Cilia - metabolism

Zebrafish - genetics

Microscopy, Confocal

Animals

Flagella - metabolism

Zebrafish - metabolism

Embryo, Nonmammalian

Zebrafish Proteins - genetics

Melanosomes - metabolism

Epinephrine - pharmacology

Details

Title: Subtitle: Bardet-Biedl syndrome genes are important in retrograde intracellular trafficking and Kupffer's vesicle cilia function
Creators: Hsan-Jan Yen - Howard Hughes Medical Institute, University of Iowa, Iowa City, IA 52242, USA
Marwan K Tayeh
Robert F Mullins
Edwin M Stone
Val C Sheffield
Diane C Slusarski
Resource Type: Journal article
Publication Details: Human molecular genetics, Vol.15(5), pp.667-677
DOI: 10.1093/hmg/ddi468
PMID: 16399798
NLM abbreviation: Hum Mol Genet
ISSN: 0964-6906
eISSN: 1460-2083
Publisher: England
Grant note: R03 HD045488-01 / NICHD NIH HHS P50-HL-55006 / NHLBI NIH HHS R01 CA112369 / NCI NIH HHS R01-EY-11298 / NEI NIH HHS
Language: English
Date published: 03/01/2006
Academic Unit: Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Medical Genetics and Genomics; Biology; Ophthalmology and Visual Sciences
Record Identifier: 9983980063902771

Metrics

35 Record Views

154 Times Cited - Web of Science