TRP channels of various metazoans mediate nearly every sensory modality, including thermal, mechanical, visual and chemical (i.e., taste and vomeronasal). A gain-of-function mutation in the Trpml3 gene causes deafness and other defects in the Varitint-waddler mouse. We have found that Trpml3 is expressed in hair cells of the inner ear as well as in another type of primary sensory neuron. The long-term goal of this research is to determine what the function of Trpml3 is in two types of sensory receptor cells. I propose to determine the function of Trpml3 in these sensory cells using a Trpml3 conditional knockout mouse I have made. I will generate mice in which Trpml3 is conditionally deleted in hair cells (before and after their development), as well as mice in which Trpml3 is deleted in other sensory neurons. I will then determine the effects of Trpml3 deletion on the anatomy of hair cells and sensory neurons (using light and scanning electron microscopy) and on their sensory function (using behavioral as well as physiological tests such as Auditory Brainstem Responses). Theses studies aim to elucidate Trpml3's function within sensory cells of the inner ear and in other primary sensory neurons.

Public Health Relevance

Currently there is still much to be learned about the auditory process in the ear and in other sensory organs. When the molecular components and their functions in sensory processing is more thoroughly understood it will lead to a better understanding of all how all the mechanisms work together in order to mediate sensory transduction and elicit appropriate responses, which will lead to better prevention, diagnosis and treatment in sensory disorders.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
5F31DC010529-03
Application #
8196799
Study Section
Special Emphasis Panel (ZDC1-SRB-L (44))
Program Officer
Sklare, Dan
Project Start
2009-12-01
Project End
2012-11-30
Budget Start
2011-12-01
Budget End
2012-11-30
Support Year
3
Fiscal Year
2012
Total Cost
$33,850
Indirect Cost
Name
Northwestern University at Chicago
Department
Anesthesiology
Type
Schools of Medicine
DUNS #
005436803
City
Chicago
State
IL
Country
United States
Zip Code
60611
Castiglioni, Andrew J; Remis, Natalie N; Flores, Emma N et al. (2011) Expression and vesicular localization of mouse Trpml3 in stria vascularis, hair cells, and vomeronasal and olfactory receptor neurons. J Comp Neurol 519:1095-114