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 are currently outcrossing each of the mutations onto different genetic backgrounds. To identify their molecular identity we are in the process of analysing large segregating intersubspecific intercrosses. The molecular cloning of these mutations should give us new insights in the development and function of the mammalian cochlea. - inner ear, circling, hearing loss, genetics,

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Intramural Research (Z01)
Project #
1Z01DC000056-01
Application #
6227915
Study Section
Special Emphasis Panel (LMG)
Project Start
Project End
Budget Start
Budget End
Support Year
1
Fiscal Year
1999
Total Cost
Indirect Cost
Name
National Institute on Deafness and Other Communication Disorders
Department
Type
DUNS #
City
State
Country
United States
Zip Code
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
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Atiba-Davies, Margaret; Noben-Trauth, Konrad (2007) TRPML3 and hearing loss in the varitint-waddler mouse. Biochim Biophys Acta 1772:1028-31
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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

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