Abstract

The molecular function of the auditory and vestibular system in the mouse is the central theme in the Section on Murine Genetics. Spontaneous mutations that cause balance dysfunction and hearing loss are ideal tools to identify genes important for the functioning of the inner ear and to elucidate their role in these sensory systems. Towards this end we concentrated our efforts on three deafness mutations: jackson circler (jc), jerker (je) and Varitint-waddler (Va). By auditory-evoked brain stem response analyses we showed that in these strains hearing impairment is completely penetrant and fully expressed in three to four week old animals. The vestibular phenotype is also fully expressed in je and Va mutants, but seems to vary in jc. To search for hearing and balance modifiers we outcrossed each of the mutations onto different genetic backgrounds. To identify their molecular identity we analyzed large segregating intersubspecific intercrosses. We constructed physical BAC contigs for each of the mutated loci and we evaluated candidate genes. The molecular cloning of these mutations should give us new insights in the development and function of the mammalian cochlea.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Intramural Research (Z01)
Project #
1Z01DC000056-03
Application #
6531855
Study Section
(LMB)
Project Start
Project End
Budget Start
Budget End
Support Year
3
Fiscal Year
2001
Total Cost
Indirect Cost

  Institution

Name
Deafness & Other Communication Disorders
Department
Type
DUNS #
City
State
Country
United States
Zip Code

  Publications

van Aken, Alexander F J; Atiba-Davies, Margaret; Marcotti, Walter et al. (2008) TRPML3 mutations cause impaired mechano-electrical transduction and depolarization by an inward-rectifier cation current in auditory hair cells of varitint-waddler mice. J Physiol 586:5403-18
Sliwinska-Kowalska, Mariola; Noben-Trauth, Konrad; Pawelczyk, Malgorzata et al. (2008) Single nucleotide polymorphisms in the cadherin 23 (CDH23) gene in Polish workers exposed to industrial noise. Am J Hum Biol 20:481-3
Chen, Zheng; Montcouquiol, Mireille; Calderon, Rene et al. (2008) Jxc1/Sobp, encoding a nuclear zinc finger protein, is critical for cochlear growth, cell fate, and patterning of the organ of corti. J Neurosci 28:6633-41
Noben-Trauth, Konrad; Neely, Harold; Brady, Roscoe O (2007) Normal hearing in alpha-galactosidase A-deficient mice, the mouse model for Fabry disease. Hear Res 234:10-4
Atiba-Davies, Margaret; Noben-Trauth, Konrad (2007) TRPML3 and hearing loss in the varitint-waddler mouse. Biochim Biophys Acta 1772:1028-31
Calderon, Alfredo; Derr, Adam; Stagner, Barden B et al. (2006) Cochlear developmental defect and background-dependent hearing thresholds in the Jackson circler (jc) mutant mouse. Hear Res 221:44-58
Johnson, Kenneth R; Zheng, Qing Yin; Noben-Trauth, Konrad (2006) Strain background effects and genetic modifiers of hearing in mice. Brain Res 1091:79-88
Drayton, Meghan; Noben-Trauth, Konrad (2006) Mapping quantitative trait loci for hearing loss in Black Swiss mice. Hear Res 212:128-39
Rzadzinska, Agnieszka; Schneider, Mark; Noben-Trauth, Konrad et al. (2005) Balanced levels of Espin are critical for stereociliary growth and length maintenance. Cell Motil Cytoskeleton 62:157-65
Rzadzinska, Agnieszka K; Derr, Adam; Kachar, Bechara et al. (2005) Sustained cadherin 23 expression in young and adult cochlea of normal and hearing-impaired mice. Hear Res 208:114-21

Showing the most recent 10 out of 18 publications