Prevention of auditory dysfunction in hypothyroid Tshr mutant mice by thyroxin treatment during development

Pamela M. Sprenkle, JoAnn McGee, John M Bertoni, Edward J. Walsh

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

Based on previous work, it is clear that genetically hypothyroid Tshrhyt mutant mice are congenitally deaf [O'Malley et al. (1995) Hear. Res. 88: 181-189, Sprinkle et al. 2001b, J. Assoc. Res. Otolaryngol. DOI: 10.1007/s101620010077]. However, the extent to which auditory development is dependent on the availability of thyroxin (T4) during specific developmental stages is unknown. The aim of this study was to determine the relative importance of prenatal and postnatal thyroxin on the ontogeny of hearing in the hyt mouse. Experimental hypothyroid subjects were offspring of hyt/hyt breeders implanted with T4 or placebo controlled-release pellets 14 days prior to mating. Pups received T4 or saline placebo injections from birth through postnatal day 14 (P14) or the time of testing on P28. In the absence of exogenous T4 replacement, very high stimulus levels (>80 dB SPL) were required to elicit responses. Remarkably, T4 treatment confined to the postnatal period failed to significantly improve auditory function relative to untreated animals, while response thresholds, latencies, and amplitudes of mice born to dams that received T4 during pregnancy were significantly improved relative to both of the untreated groups. Response thresholds were improved somewhat when maternal T4 replacement was followed by treatment during the first 14 days of life, and animals treated throughout prenatal and postnatal life were comparable to those of age-matched euthyroid individuals. Findings from this study show that treatment of hyt/hyt mice with exogenous T4 significantly attenuates hypothyroid-induced otopathology in a developmental-stage-dependent manner. In addition, we demonstrate that postnatal development is critically dependent on prenatal exposure to thyroxin and that the critical window of T4 dependence extends throughout development.

Original languageEnglish (US)
Pages (from-to)348-361
Number of pages14
JournalJARO - Journal of the Association for Research in Otolaryngology
Volume2
Issue number4
DOIs
Publication statusPublished - Dec 1 2001

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Keywords

  • Deafness
  • Development
  • Hearing
  • Hypothyroidism
  • Maturation
  • Thyrotropin

ASJC Scopus subject areas

  • Otorhinolaryngology
  • Sensory Systems

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