The long-term goal of my laboratory is to elucidate the mechanisms that regulate the development and function of the auditory sense organ and how inner ear defects cause hearing loss. We propose here to study the function of the Ig-superfamily member neuroplastin (Nptn) in the inner ear. Based on our preliminary data we hypothesize that Nptn regulates hair cell function and their interactions with sensory afferent neurons by mechanisms that are regulated by alternative splicing of the primary Nptn transcript. To test our hypothesis, we will: (i) determine the expression pattern and subcellular localization of Nptn isoforms in the inner ear; (ii) Study the consequences of inactivation of Nptn isoforms in hair cells and afferent neurons of the inner ear for hearing function; (iii) Determine the mechanisms by which Nptn isoforms carry out their function in hair cells and afferent neurons; (iv) determine the extent to which mutations in the gene encoding NPTN and its close homologues cause hearing impairment in humans. We anticipate that our findings will reveal novel insights into the mechanisms that regulate the function of hair cells and their innervating sensory afferent neurons, and how mutations in NPTN cause disease.

Public Health Relevance

Hearing loss is a major health problem that significantly affects the life quality of affected individuals. Many forms of hearing loss are of genetic origin and affect the inner ear. We propose here to investigate the mechanisms by which mutations in a transmembrane receptor that is expressed in the inner ear causes deafness.

National Institute of Health (NIH)
National Institute on Deafness and Other Communication Disorders (NIDCD)
Research Project (R01)
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Auditory System Study Section (AUD)
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Cyr, Janet
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Johns Hopkins University
Schools of Medicine
United States
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