Ciliopathy is differentially distributed in the brain of a Bardet-Biedl syndrome mouse model

Khristofor Agassandian; Milan Patel; Marianna Agassandian; Karina E Steren; Kamal Rahmouni; Val C Sheffield; J Patrick Card

doi:10.1371/journal.pone.0093484

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Ciliopathy is differentially distributed in the brain of a Bardet-Biedl syndrome mouse model

Journal article

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Ciliopathy is differentially distributed in the brain of a Bardet-Biedl syndrome mouse model

Khristofor Agassandian, Milan Patel, Marianna Agassandian, Karina E Steren, Kamal Rahmouni, Val C Sheffield and J Patrick Card

PloS one, Vol.9(4), pp.e93484-e93484

2014

DOI: 10.1371/journal.pone.0093484

PMCID: PMC3973560

PMID: 24695551

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Abstract

Bardet-Biedl syndrome (BBS) is a genetically heterogeneous inherited human disorder displaying a pleotropic phenotype. Many of the symptoms characterized in the human disease have been reproduced in animal models carrying deletions or knock-in mutations of genes causal for the disorder. Thinning of the cerebral cortex, enlargement of the lateral and third ventricles, and structural changes in cilia are among the pathologies documented in these animal models. Ciliopathy is of particular interest in light of recent studies that have implicated primary neuronal cilia (PNC) in neuronal signal transduction. In the present investigation, we tested the hypothesis that areas of the brain responsible for learning and memory formation would differentially exhibit PNC abnormalities in animals carrying a deletion of the Bbs4 gene (Bbs4-/-). Immunohistochemical localization of adenylyl cyclase-III (ACIII), a marker restricted to PNC, revealed dramatic alterations in PNC morphology and a statistically significant reduction in number of immunopositive cilia in the hippocampus and amygdala of Bbs4-/- mice compared to wild type (WT) littermates. Western blot analysis confirmed the decrease of ACIII levels in the hippocampus and amygdala of Bbs4-/- mice, and electron microscopy demonstrated pathological alterations of PNC in the hippocampus and amygdala. Importantly, no neuronal loss was found within the subregions of amygdala and hippocampus sampled in Bbs4-/- mice and there were no statistically significant alterations of ACIII immunopositive cilia in other areas of the brain not known to contribute to the BBS phenotype. Considered with data documenting a role of cilia in signal transduction these findings support the conclusion that alterations in cilia structure or neurochemical phenotypes may contribute to the cognitive deficits observed in the Bbs4-/- mouse mode.

Cilia - pathology

Bardet-Biedl Syndrome - metabolism

Microtubule-Associated Proteins - metabolism

Amygdala - metabolism

Male

Hippocampus - pathology

Adenylyl Cyclases - metabolism

Amygdala - pathology

Cilia - metabolism

Hippocampus - metabolism

Animals

Bardet-Biedl Syndrome - pathology

Mice

Disease Models, Animal

Details

Title: Subtitle: Ciliopathy is differentially distributed in the brain of a Bardet-Biedl syndrome mouse model
Creators: Khristofor Agassandian - Department of Neuroscience, the University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America
Milan Patel - Department of Neuroscience, the University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America
Marianna Agassandian - Department of Medicine, the University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America
Karina E Steren - Department of Neuroscience, the University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America
Kamal Rahmouni - Departments of Pharmacology and Internal Medicine, the University of Iowa, Iowa City, Iowa, United States of America
Val C Sheffield - Department of Pediatrics, the University of Iowa, Iowa City, Iowa, United States of America; Howard Hughes Medical Institute, University of Iowa, Iowa City, Iowa, United States of America
J Patrick Card - Department of Neuroscience, the University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America
Resource Type: Journal article
Publication Details: PloS one, Vol.9(4), pp.e93484-e93484
DOI: 10.1371/journal.pone.0093484
PMID: 24695551
PMCID: PMC3973560
NLM abbreviation: PLoS One
ISSN: 1932-6203
eISSN: 1932-6203
Publisher: Public Library of Science; United States
Grant note: R01 EY011298 / NEI NIH HHS P01HL084207 / NHLBI NIH HHS Howard Hughes Medical Institute 1R01HL093134 / NHLBI NIH HHS R01 EY017168 / NEI NIH HHS R01 HL093134 / NHLBI NIH HHS R01 NS083543 / NINDS NIH HHS P01 HL084207 / NHLBI NIH HHS R01-EY-11298 / NEI NIH HHS
Language: English
Date published: 2014
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: 9984040382302771

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