Article

Dietary thyroid hormone replacement ameliorates hearing deficits in hypothyroid mice.

Department of Human Genetics, University of Michigan Medical School, Ann Arbor, Michigan 48109-0618, USA.
Mammalian Genome (impact factor: 2.89). 09/2007; 18(8):596-608. DOI:10.1007/s00335-007-9038-0 pp.596-608
Source: PubMed

ABSTRACT Thyroid hormone (TH) insufficiency causes variable hearing impairment and mental deficiency in humans. Rodents lacking TH have congenital hearing deficiency that has been attributed to physiologic, morphologic, and developmental abnormalities of the auditory system. We examined four genetically defined strains of hypothyroid mice for development of hearing and response to TH replacement initiated during late gestation and continued through six weeks of age. Auditory brain stem response studies showed variable hearing impairment in homozygous mutants of each strain at three weeks of age relative to normal littermates. Mutants from three of the strains still had hearing deficiencies at six weeks of age. TH-enriched diet significantly improved hearing in three-week-old mutants of each strain relative to untreated mutants. Differences in the level of hearing impairment between the Prop1df and Pit1dw mutants, which have defects in the same developmental pathway, were determined to be due to genetic background modifier genes. Further physiologic and morphologic studies in the Cgatm1Sac strain indicated that poor hearing was due to cochlear defects. We conclude that TH supplement administered during the critical period of hearing development in mice can prevent deafness associated with congenital hypothyroidism of heterogeneous genetic etiology.

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Keywords

Auditory brain
 
auditory system
 
Cgatm1Sac strain
 
cochlear defects
 
congenital hypothyroidism
 
developmental abnormalities
 
developmental pathway
 
genetic background modifier genes
 
hearing development
 
hearing impairment
 
heterogeneous genetic etiology
 
homozygous mutants
 
hypothyroid mice
 
Pit1dw mutants
 
strains
 
TH supplement
 
three-week-old mutants
 
Thyroid hormone
 
untreated mutants
 
variable hearing impairment
 

I Jill Karolyi