Ectopic expression of human BBS4 can rescue Bardet-Biedl syndrome phenotypes in Bbs4 null mice

Xitiz Chamling; Seongjin Seo; Kevin Bugge; Charles Searby; Deng F Guo; Arlene V Drack; Kamal Rahmouni; Val C Sheffield

doi:10.1371/journal.pone.0059101

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Ectopic expression of human BBS4 can rescue Bardet-Biedl syndrome phenotypes in Bbs4 null mice

Journal article

Open access

Peer reviewed

Ectopic expression of human BBS4 can rescue Bardet-Biedl syndrome phenotypes in Bbs4 null mice

Xitiz Chamling, Seongjin Seo, Kevin Bugge, Charles Searby, Deng F Guo, Arlene V Drack, Kamal Rahmouni and Val C Sheffield

PloS one, Vol.8(3), pp.e59101-e59101

2013

DOI: 10.1371/journal.pone.0059101

PMCID: PMC3598656

PMID: 23554981

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Abstract

Bardet-Biedl syndrome (BBS) is a genetically heterogeneous autosomal recessive disorder characterized by obesity, retinal degeneration, polydactyly, hypogenitalism and renal defects. Recent findings have associated the etiology of the disease with cilia, and BBS proteins have been implicated in trafficking various ciliary cargo proteins. To date, 17 different genes have been reported for BBS among which BBS1 is the most common cause of the disease followed by BBS10, and BBS4. A murine model of Bbs4 is known to phenocopy most of the human BBS phenotypes, and it is being used as a BBS disease model. To better understand the in vivo localization, cellular function, and interaction of BBS4 with other proteins, we generated a transgenic BBS4 mouse expressing the human BBS4 gene under control of the beta actin promoter. The transgene is expressed in various tissues including brain, eye, testis, heart, kidney, and adipose tissue. These mice were further bred to express the transgene in Bbs4 null mice, and their phenotype was characterized. Here we report that despite tissue specific variable expression of the transgene, human BBS4 was able to complement the deficiency of Bbs4 and rescue all the BBS phenotypes in the Bbs4 null mice. These results provide an encouraging prospective for gene therapy for BBS related phenotypes and potentially for other ciliopathies.

Retinal Diseases - genetics

Testis - metabolism

Bardet-Biedl Syndrome - metabolism

Humans

Leptin - metabolism

Male

Obesity - genetics

Sympathetic Nervous System - metabolism

Infertility, Male - genetics

Bardet-Biedl Syndrome - genetics

Female

Hydrocephalus - genetics

Transgenes

Disease Models, Animal

Gene Expression

Genotype

Mice, Transgenic

Cilia - metabolism

Mice, Knockout

Proteins - genetics

Phenotype

Animals

Proteins - metabolism

Kidney - innervation

Mice

Details

Title: Subtitle: Ectopic expression of human BBS4 can rescue Bardet-Biedl syndrome phenotypes in Bbs4 null mice
Creators: Xitiz Chamling - Department of Pediatrics, University of Iowa Interdisciplinary Program of Genetics, Iowa City, Iowa, USA
Seongjin Seo
Kevin Bugge
Charles Searby
Deng F Guo
Arlene V Drack
Kamal Rahmouni
Val C Sheffield
Resource Type: Journal article
Publication Details: PloS one, Vol.8(3), pp.e59101-e59101
DOI: 10.1371/journal.pone.0059101
PMID: 23554981
PMCID: PMC3598656
NLM abbreviation: PLoS One
ISSN: 1932-6203
eISSN: 1932-6203
Publisher: United States
Grant note: R01EY022616 / NEI NIH HHS R01 EY011298 / NEI NIH HHS R01EY110298 / NEI NIH HHS R01 EY022616 / NEI NIH HHS Howard Hughes Medical Institute R01 EY017168 / NEI NIH HHS R01 NS083543 / NINDS NIH HHS P01 HL084207 / NHLBI NIH HHS R01EY017168 / NEI NIH HHS
Language: English
Date published: 2013
Academic Unit: Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Medical Genetics and Genomics; Neuroscience and Pharmacology; Internal Medicine; Ophthalmology and Visual Sciences
Record Identifier: 9983979976002771

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