This research was supported by National Institute of Hospitals grant R21 DC010424 given to Tina Jaskoll and Michael Melnick.
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Original Article
An in vitro mouse model of congenital cytomegalovirus-induced pathogenesis of the inner ear cochlea
Article first published online: 26 DEC 2012
DOI: 10.1002/bdra.23105
Copyright © 2012 Wiley Periodicals, Inc.
Issue
Birth Defects Research Part A: Clinical and Molecular Teratology
Volume 97, Issue 2, pages 69–78, February 2013
Additional Information
How to Cite
Melnick, M. and Jaskoll, T. (2013), An in vitro mouse model of congenital cytomegalovirus-induced pathogenesis of the inner ear cochlea. Birth Defects Research Part A: Clinical and Molecular Teratology, 97: 69–78. doi: 10.1002/bdra.23105
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This research was supported by National Institute of Hospitals grant R21 DC010424 given to Tina Jaskoll and Michael Melnick.
Publication History
- Issue published online: 11 FEB 2013
- Article first published online: 26 DEC 2012
- Manuscript Accepted: 6 NOV 2012
- Manuscript Revised: 22 OCT 2012
- Manuscript Received: 15 AUG 2012
- Abstract
- Article
- References
- Cited By
Keywords:
- congenital cytomegalovirus infection;
- sensorineural hearing loss;
- in vitro mouse model;
- cochlear pathogenesis
Abstract
Congenital human cytomegalovirus (CMV) infection is the leading nongenetic etiology of sensorineural hearing loss (SNHL) at birth and prelingual SNHL not expressed at birth. The paucity of temporal bone autopsy specimens from infants with congenital CMV infection has hindered the critical correlation of histopathology with pathogenesis. Here, we present an in vitro embryonic mouse model of CMV-infected cochleas that mimics the human sites of viral infection and associated pathology. There is a striking dysplasia/hyperplasia in mouse CMV-infected cochlear epithelium and mesenchyme, including organ of Corti hair and supporting cells and stria vascularis. This is concomitant with significant dysregulation of p19, p21, p27, and Pcna gene expression, as well as proliferating cell nuclear antigen (PCNA) protein expression. Other pathologies similar to those arising from known deafness gene mutations include downregulation of KCNQ1 protein expression in the stria vascularis, as well as hypoplastic and dysmorphic melanocytes. Thus, this model provides a relevant and reliable platform within which the detailed cell and molecular biology of CMV-induced deafness may be studied. Birth Defects Research (Part A), 2013. © 2012 Wiley Periodicals, Inc.