QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, January 28, 2009, 29(4):1212-1223; doi:10.1523/JNEUROSCI.4957-08.2009

This Article Full Text Full Text (PDF) Supplemental Data Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Mustapha, M. Articles by Duncan, R. K. Search for Related Content PubMed PubMed Citation Articles by Mustapha, M. Articles by Duncan, R. K. Pubmed/NCBI databases Gene GEO Profiles HomoloGene Protein UniGene Medline Plus Health Information Hearing Disorders and Deafness

 Previous Article  |  Next Article 

Development/Plasticity/Repair
Deafness and Permanently Reduced Potassium Channel Gene Expression and Function in Hypothyroid Pit1^dw Mutants

Mirna Mustapha,¹ Qing Fang,¹ Tzy-Wen Gong,² David F. Dolan,² Yehoash Raphael,² Sally A. Camper,¹ and R. Keith Duncan²

Departments of ¹Human Genetics and ²Otolaryngology, University of Michigan Medical School, Ann Arbor, Michigan 48109-5618

Correspondence should be addressed to Sally A. Camper, Department of Human Genetics, University of Michigan Medical School, 4909 Buhl Building, 1241 Catherine Street, Ann Arbor, MI 48109-5618. Email: scamper{at}umich.edu

The absence of thyroid hormone (TH) during late gestation and early infancy can cause irreparable deafness in both humans and rodents. A variety of rodent models have been used in an effort to identify the underlying molecular mechanism. Here, we characterize a mouse model of secondary hypothyroidism, pituitary transcription factor 1 (Pit1^dw), which has profound, congenital deafness that is rescued by oral TH replacement. These mutants have tectorial membrane abnormalities, including a prominent Hensen's stripe, elevated β-tectorin composition, and disrupted striated-sheet matrix. They lack distortion product otoacoustic emissions and cochlear microphonic responses, and exhibit reduced endocochlear potentials, suggesting defects in outer hair cell function and potassium recycling. Auditory system and hair cell physiology, histology, and anatomy studies reveal novel defects of hormone deficiency related to deafness: (1) permanently impaired expression of KCNJ10 in the stria vascularis of Pit1^dw mice, which likely contributes to the reduced endocochlear potential, (2) significant outer hair cell loss in the mutants, which may result from cellular stress induced by the lower KCNQ4 expression and current levels in Pit1^dw mutant outer hair cells, and (3) sensory and strial cell deterioration, which may have implications for thyroid hormone dysregulation in age-related hearing impairment. In summary, we suggest that these defects in outer hair cell and strial cell function are important contributors to the hearing impairment in Pit1^dw mice.

Key words: secondary hypothyroidism; tectorial membrane; KCNQ1; KCNQ4; KCNJ10; prestin; POU1F1

---

Received Oct. 14, 2008; revised Dec. 12, 2008; accepted Dec. 19, 2008.

Correspondence should be addressed to Sally A. Camper, Department of Human Genetics, University of Michigan Medical School, 4909 Buhl Building, 1241 Catherine Street, Ann Arbor, MI 48109-5618. Email: scamper{at}umich.edu

This article has been cited by other articles:

				A. A. Zdebik, P. Wangemann, and T. J. Jentsch Potassium Ion Movement in the Inner Ear: Insights from Genetic Disease and Mouse Models Physiology, October 1, 2009; 24(5): 307 - 316. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help