Cochlear structure and hearing in murine congenital hypothyroidism caused by targeted gene mutations in the mouse dual oxidase A1 and A2 genes

Kedar Kakodkar, Miriam Saadia-Redleaf, Mia Weiss, Helmut Grasberger

Research output: Contribution to journalArticlepeer-review

Abstract

Objective: The aim of the project is to investigate congenital hypothyroidism via targeted DUOXA1/2 gene deletion and resultant hearing impairment by analysis of auditory brainstem response and cochlear histopathology. Methods: Congenitally hypothyroid mice with targeted DUOXA1/2 gene deletions of different age groups were studied. Twenty-two knockout and wild type mice were sedated in order to perform auditory brainstem response testing, Cochlear histopathology was also reviewed. Results: There was no significant difference noted between wild type and knock out mice of varying ages with regards to cochlear histopathology and auditory brainstem response. Conclusion: The targeted deletion used is a new mouse model and functions by disrupting two genes simultaneously: Dual oxidase maturation factor 1 and 2. The knock-out mice developed provide a model for complete functional deficiency of the dual oxidases. Such mice display essentially no iodide organification within the thyroid and subsequently undetectable serum T4. Since such a severe defect in hormonogenesis would occur, we expect to encounter sequelae of congenital hypothyroidism, such as hearing impairment. From this study, we have noted no significant difference between wild type and knock out mice with regards to auditory brainstem response testing and cochlear histopathology.

Original languageEnglish
Pages (from-to)S324
JournalLaryngoscope
Volume121
Issue numberSUPPL. 5
DOIs
StatePublished - 2011
Externally publishedYes

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