Document Detail

Sox2 and JAGGED1 expression in normal and drug-damaged adult mouse inner ear.
MedLine Citation:
PMID:  18157569     Owner:  NLM     Status:  MEDLINE    
Inner ear hair cells detect environmental signals associated with hearing, balance, and body orientation. In humans and other mammals, significant hair cell loss leads to irreversible hearing and balance deficits, whereas hair cell loss in nonmammalian vertebrates is repaired by the spontaneous generation of replacement hair cells. Research in mammalian hair cell regeneration is hampered by the lack of in vivo damage models for the adult mouse inner ear and the paucity of cell-type-specific markers for non-sensory cells within the sensory receptor epithelia. The present study delineates a protocol to drug damage the adult mouse auditory epithelium (organ of Corti) in situ and uses this protocol to investigate Sox2 and Jagged1 expression in damaged inner ear sensory epithelia. In other tissues, the transcription factor Sox2 and a ligand member of the Notch signaling pathway, Jagged1, are involved in regenerative processes. Both are involved in early inner ear development and are expressed in developing support cells, but little is known about their expressions in the adult. We describe a nonsurgical technique for inducing hair cell damage in adult mouse organ of Corti by a single high-dose injection of the aminoglycoside kanamycin followed by a single injection of the loop diuretic furosemide. This drug combination causes the rapid death of outer hair cells throughout the cochlea. Using immunocytochemical techniques, Sox2 is shown to be expressed specifically in support cells in normal adult mouse inner ear and is not affected by drug damage. Sox2 is absent from auditory hair cells, but is expressed in a subset of vestibular hair cells. Double-labeling experiments with Sox2 and calbindin suggest Sox2-positive hair cells are Type II. Jagged1 is also expressed in support cells in the adult ear and is not affected by drug damage. Sox2 and Jagged1 may be involved in the maintenance of support cells in adult mouse inner ear.
Elizabeth C Oesterle; Sean Campbell; Ruth R Taylor; Andrew Forge; Clifford R Hume
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2007-12-22
Journal Detail:
Title:  Journal of the Association for Research in Otolaryngology : JARO     Volume:  9     ISSN:  1438-7573     ISO Abbreviation:  J. Assoc. Res. Otolaryngol.     Publication Date:  2008 Mar 
Date Detail:
Created Date:  2008-03-03     Completed Date:  2009-04-30     Revised Date:  2013-06-06    
Medline Journal Info:
Nlm Unique ID:  100892857     Medline TA:  J Assoc Res Otolaryngol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  65-89     Citation Subset:  IM    
Virginia Merrill Bloedel Hearing Research Center, Department of Otolaryngology-Head and Neck Surgery, University of Washington, CHDD CD176, Box 357923, Seattle, WA 98195-7923, USA.
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MeSH Terms
Animals, Newborn
Anti-Bacterial Agents / toxicity
Biological Markers / metabolism
Calcium-Binding Proteins / metabolism*
Cochlear Diseases / chemically induced
Disease Models, Animal
Diuretics / toxicity
Furosemide / toxicity
Intercellular Signaling Peptides and Proteins / metabolism*
Kanamycin / toxicity
Membrane Proteins / metabolism*
Mice, Inbred CBA
Organ of Corti / drug effects,  metabolism*
SOXB1 Transcription Factors / metabolism*
Time Factors
Grant Support
G27//Action on Hearing Loss; P30DC04661/DC/NIDCD NIH HHS; P30HD002274/HD/NICHD NIH HHS; R01DC03944/DC/NIDCD NIH HHS
Reg. No./Substance:
0/Anti-Bacterial Agents; 0/Biological Markers; 0/Calcium-Binding Proteins; 0/Diuretics; 0/Intercellular Signaling Peptides and Proteins; 0/Membrane Proteins; 0/SOXB1 Transcription Factors; 0/Sox2 protein, mouse; 134324-36-0/Serrate proteins; 54-31-9/Furosemide; 59-01-8/Kanamycin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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