| Alström Syndrome protein ALMS1 localizes to basal bodies of cochlear hair cells and regulates cilium-dependent planar cell polarity. | |
| | |
MedLine Citation:
|
PMID: 21071598 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Alström Syndrome is a life-threatening disease characterized primarily by numerous metabolic abnormalities, retinal degeneration, cardiomyopathy, kidney and liver disease, and sensorineural hearing loss. The cellular localization of the affected protein, ALMS1, has suggested roles in ciliary function and/or ciliogenesis. We have investigated the role of ALMS1 in the cochlea and the pathogenesis of hearing loss in Alström Syndrome. In neonatal rat organ of Corti, ALMS1 was localized to the basal bodies of hair cells and supporting cells. ALMS1 was also evident at the basal bodies of differentiating fibrocytes and marginal cells in the lateral wall. Centriolar ALMS1 expression was retained into maturity. In Alms1-disrupted mice, which recapitulate the neurosensory deficits of human Alström Syndrome, cochleae displayed several cyto-architectural defects including abnormalities in the shape and orientation of hair cell stereociliary bundles. Developing hair cells were ciliated, suggesting that ciliogenesis was largely normal. In adult mice, in addition to bundle abnormalities, there was an accelerated loss of outer hair cells and the progressive appearance of large lesions in stria vascularis. Although the mice progressively lost distortion product otoacoustic emissions, suggesting defects in outer hair cell amplification, their endocochlear potentials were normal, indicating the strial atrophy did not affect its function. These results identify previously unrecognized cochlear histopathologies associated with this ciliopathy that (i) implicate ALMS1 in planar cell polarity signaling and (ii) suggest that the loss of outer hair cells causes the majority of the hearing loss in Alström Syndrome. |
| | |
Authors:
|
Daniel Jagger; Gayle Collin; John Kelly; Emily Towers; Graham Nevill; Chantal Longo-Guess; Jennifer Benson; Karin Halsey; David Dolan; Jan Marshall; Jürgen Naggert; Andrew Forge |
Related Documents
:
|
8034748 - Association of basonuclin with ability of keratinocytes to multiply and with absence of... 9481798 - The vestibular hair cells: post-transductional signal processing. 16237318 - Heteromerization and colocalization of trpv1 and trpv2 in mammalian cell lines and rat ... 10561418 - Regional distribution of ionic currents and membrane voltage responses of type ii hair ... 9629588 - Distribution of endocrine cells in the gut of the impala (aepyceros melampus). 3421018 - The cytologic identification and quantification of testicular cell subtypes. reproducib... |
Publication Detail:
|
Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2010-11-11 |
Journal Detail:
|
Title: Human molecular genetics Volume: 20 ISSN: 1460-2083 ISO Abbreviation: Hum. Mol. Genet. Publication Date: 2011 Feb |
Date Detail:
|
Created Date: 2011-01-07 Completed Date: 2011-07-19 Revised Date: 2012-02-01 |
Medline Journal Info:
|
Nlm Unique ID: 9208958 Medline TA: Hum Mol Genet Country: England |
Other Details:
|
Languages: eng Pagination: 466-81 Citation Subset: IM |
Affiliation:
|
UCL Ear Institute, University College London, 332 Gray’s Inn Road, London WC1X 8EE, UK. d.jagger@ucl.ac.uk |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Alstrom Syndrome
/
genetics,
metabolism*,
pathology* Animals Cell Differentiation Cell Polarity Centrioles Cilia / ultrastructure Cochlea / ultrastructure* DNA-Binding Proteins / genetics, metabolism* Fluorescent Antibody Technique Hair Cells, Auditory / metabolism*, ultrastructure* Hearing Loss / genetics*, metabolism, pathology* Mice Mice, Knockout Microscopy, Electron Organ of Corti / ultrastructure Rats Rats, Sprague-Dawley Signal Transduction Stria Vascularis / ultrastructure |
| Grant Support | |
ID/Acronym/Agency:
|
BB/D009669/1//Biotechnology and Biological Sciences Research Council; DC04301/DC/NIDCD NIH HHS; HD036878/HD/NICHD NIH HHS; P30 DC05188/DC/NIDCD NIH HHS; R01 HD036878-13/HD/NICHD NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/Alms1 protein, mouse; 0/DNA-Binding Proteins |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Signals mediating skeletal muscle remodeling by resistance exercise: PI3-kinase independent activati...
Next Document: Manipulating broad-spectrum disease resistance by suppressing pathogen-induced auxin accumulation in...