Link to the University of Pittsburgh Homepage
Link to the University Library System Homepage Link to the Contact Us Form

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

Agassandian, K and Patel, M and Agassandian, M and Steren, KE and Rahmouni, K and Sheffield, VC and Card, JP (2014) Ciliopathy is differentially distributed in the brain of a Bardet-Biedl syndrome mouse model. PLoS ONE, 9 (4).

Published Version
Available under License : See the attached license file.

Download (4MB) | Preview
[img] Plain Text (licence)
Available under License : See the attached license file.

Download (1kB)


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. © 2014 Agassandian et al.


Social Networking:
Share |


Item Type: Article
Status: Published
CreatorsEmailPitt UsernameORCID
Agassandian, K
Patel, M
Agassandian, Mmaa175@pitt.eduMAA175
Steren, KE
Rahmouni, K
Sheffield, VC
Card, JPcard@pitt.eduCARD
ContributionContributors NameEmailPitt UsernameORCID
Date: 2 April 2014
Date Type: Publication
Journal or Publication Title: PLoS ONE
Volume: 9
Number: 4
DOI or Unique Handle: 10.1371/journal.pone.0093484
Schools and Programs: Dietrich School of Arts and Sciences > Neuroscience
Refereed: Yes
Date Deposited: 30 Jun 2014 15:50
Last Modified: 22 Jun 2021 12:55


Monthly Views for the past 3 years

Plum Analytics

Actions (login required)

View Item View Item