Journal article
A catechol-O-methyltransferase that is essential for auditory function in mice and humans
Proceedings of the National Academy of Sciences - PNAS, Vol.105(38), pp.14609-14614
09/23/2008
DOI: 10.1073/pnas.0807219105
PMCID: PMC2567147
PMID: 18794526
Abstract
We have identified a previously unannotated catechol-
O
-methyltranferase (COMT), here designated COMT2, through positional cloning of a chemically induced mutation responsible for a neurobehavioral phenotype. Mice homozygous for a missense mutation in
Comt2
show vestibular impairment, profound sensorineuronal deafness, and progressive degeneration of the organ of Corti. Consistent with this phenotype, COMT2 is highly expressed in sensory hair cells of the inner ear. COMT2 enzymatic activity is significantly reduced by the missense mutation, suggesting that a defect in catecholamine catabolism underlies the auditory and vestibular phenotypes. Based on the studies in mice, we have screened DNA from human families and identified a nonsense mutation in the human ortholog of the murine
Comt2
gene that causes nonsyndromic deafness. Defects in catecholamine modification by COMT have been previously implicated in the development of schizophrenia. Our studies identify a previously undescribed COMT gene and indicate an unexpected role for catecholamines in the function of auditory and vestibular sense organs.
Details
- Title: Subtitle
- A catechol-O-methyltransferase that is essential for auditory function in mice and humans
- Creators
- Xin Du - Departments of Genetics andMartin Schwander - Cell Biology, Institute for Childhood and Neglected Diseases, andEva Marie Y Moresco - Departments of Genetics andPia Viviani - Departments of Genetics andClaudia Haller - Departments of Genetics andMichael S Hildebrand - Department of Otolaryngology and the Interdepartmental Ph.D. Genetic Program, University of Iowa, 200 Hawkins Drive, Iowa City, IA 52242Kwang Pak - School of Medicine, University of California, San Diego, La Jolla, CA 92037Lisa Tarantino - Genomics Institute of the Novartis Research Foundation, San Diego, CA 92121; andAmanda Roberts - Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, La Jolla, CA 92037Heather Richardson - Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, La Jolla, CA 92037George Koob - Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, La Jolla, CA 92037Hossein Najmabadi - Genetic Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, IranAllen F Ryan - School of Medicine, University of California, San Diego, La Jolla, CA 92037Richard J. H Smith - Department of Otolaryngology and the Interdepartmental Ph.D. Genetic Program, University of Iowa, 200 Hawkins Drive, Iowa City, IA 52242Ulrich Müller - Cell Biology, Institute for Childhood and Neglected Diseases, andBruce Beutler - Departments of Genetics and
- Resource Type
- Journal article
- Publication Details
- Proceedings of the National Academy of Sciences - PNAS, Vol.105(38), pp.14609-14614
- DOI
- 10.1073/pnas.0807219105
- PMID
- 18794526
- PMCID
- PMC2567147
- NLM abbreviation
- Proc Natl Acad Sci U S A
- ISSN
- 0027-8424
- eISSN
- 1091-6490
- Publisher
- National Academy of Sciences
- Language
- English
- Date published
- 09/23/2008
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Molecular Physiology and Biophysics; Anatomy and Cell Biology; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Otolaryngology; Internal Medicine
- Record Identifier
- 9984006335402771
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