Dietary thyroid hormone replacement ameliorates hearing deficits in hypothyroid mice

被引:34
作者
Karolyi, I. Jill
Dootz, Gary A.
Halsey, Karin
Beyer, Lisa
Probst, Frank J.
Johnson, Kenneth R.
Parlow, Albert F.
Raphael, Yehoash
Dolan, David F.
Camper, Sally A.
机构
[1] Univ Michigan, Sch Med, Dept Human Genet, Ann Arbor, MI 48109 USA
[2] Univ Michigan, Sch Med, Dept Otolaryngol, Ann Arbor, MI 48109 USA
[3] Jackson Lab, Bar Harbor, ME 04609 USA
[4] Harbor UCLA Med Ctr, Torrance, CA 90509 USA
关键词
D O I
10.1007/s00335-007-9038-0
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 Prop1(df) and Pit1(dw) 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 Cga(tm1Sac) 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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页码:596 / 608
页数:13
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