Understanding Hearing Loss in Thyroid Hormone Deficient Mice

Thursday, June 21, 2007 - 1:00 p.m. to Friday, June 22, 2007 - 1:55 p.m.

Grand Rounds – Sponsored by the Department of Otolaryngology - Head and Neck Surgery

Featuring Mirna Mustapha-Chaib, Ph.D.
Post-doctoral Research Investigator
Department of Human Genetics
The University of MichiganMedicalSchool

Location: Gillespie Conference Room, 1st Floor (Building 837)
Questions can be directed to Abby Copeland at acopelan@uci.edu; 949-824-9107 

Abstract:
Thyroid hormone (TH) is fundamental to the development of normal auditory function. It acts as a ligand for regulating transcriptional activation and repression of hundreds of genes. Little is known which genes are critical targets of thyroid hormone regulated transcription in the developing cochlea. The Pit1dw mouse provides an excellent model of secondary hypothyroidism. Despite of a rather normal morphology of the sensory hair cells in the organ of Corti, Pit1dw mice exhibit profound hearing impairment, an absence of distortion product and cochlear microphonic, and reduction in endocochlear potential. Pit1dw mutant mice exhibit developmental delay in some processes, while suffering from long-lasting alterations through adulthood in other functions. For example, despite of reduced PRESTIN, which is critical for outer hair cell function, at birth, adult Pit1dw mutants express PRESTIN appropriately. In contrast, these mice exhibit permanent defects in expression of several potassium channels and neuronal markers. In addition, defects in hair cells neurogenesis, manly of the inner hair cells, may also contribute to the profound nature of hearing loss in these mice. To explore the molecular mechanism whereby TH regulates cochlear neurogenesis, we examined differences in gene expression in cochleae between normal and TH deficient mice. This microarray study uncovered several novel classes of genes that may be significant contributors in the permanent hearing loss caused by TH deficiency. In the future this work could contribute to rational design for therapeutics to improve cochlear function.