help button home button Am J Pathol PCR Enhanced. PCRboost from Biomatrica
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
A more recent version of this article appeared on August 1, 2007

Published online before print July 9, 2007
This Article
Right arrow Full Text (Rapid PDF)
Right arrow Supplemental Material
Right arrow All Versions of this Article:
ajpath.2007.070068v1
171/2/608    most recent
Right arrow Purchase Article
Right arrow View Shopping Cart
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Guipponi, M.
Right arrow Articles by Scott, H. S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Guipponi, M.
Right arrow Articles by Scott, H. S.
Copyright © 2007 American Society for Investigative Pathology
American Journal of Pathology, doi:10.2353/ajpath.2007.070068

Accepted for publication May 11, 2007.

Article

Mice Deficient for the Type II Transmembrane Serine Protease, TMPRSS1/hepsin, Exhibit Profound Hearing Loss

Michel Guipponi*, Justin Tan{dagger}{ddagger}, Ping Z.F. Cannon*, Lauren Donley{dagger}, Pauline Crewther*, Maria Clarke{ddagger}, Qingyu Wu{sect}, Robert K. Shepherd{dagger}{ddagger}, and Hamish S. Scott*@

From the Molecular Medicine Division,* The Walter and Eliza Hall Institute of Medical Research, Victoria, Australia; The Bionic Ear Institute,{dagger} East Melbourne, Victoria, Australia; Department of Otolaryngology,{ddagger} University of Melbourne, East Melbourne, Victoria, Australia; and the Department of Cardiovascular Research,{sect} Berlex Biosciences, Richmond, California

@ To whom correspondence should be addressed. E-mail: hscott{at}wehi.edu.au.


  Abstract

Defective proteolysis has been implicated in hearing loss through the discovery of mutations causing autosomal recessive nonsyndromic deafness in a type II transmembrane serine protease gene, TMPRSS3. To investigate their physiological function and the contribution of this family of proteases to the auditory function, we analyzed the hearing status of mice deficient for hepsin, also known as TMPRSS1. These mice exhibited profound hearing loss with elevated hearing thresholds compared with their heterozygous and wild-type littermates. Their cochleae showed abnormal tectorial membrane development, reduction in fiber compaction in the peripheral portion of the auditory nerve, and decreased expression of the myelin proteins myelin basic protein and myelin protein zero. In addition, reduced level of the large conductance voltage- and Ca2+-activated K+ channel was detected in the sensory hair cells of Tmprss1-null mice. We examined thyroid hormone levels in Tmprss1-deficient mice, as similar cochlear defects have been reported in animal models of hypothyroidism, and found significantly reduced free thyroxine levels. These data show that TMPRSS1 is required for normal auditory function. Hearing impairment present in Tmprss1-null mice is characterized by a combination of various structural, cellular, and molecular abnormalities that are likely to affect different cochlear processes.






HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Copyright © 2007 by the American Society for Investigative Pathology.