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
Department of Human Genetics, University of Michigan Medical School, Ann Arbor, Michigan 48109-0618, USA.
Mamm Genome. 2007 Aug;18(8):596-608. doi: 10.1007/s00335-007-9038-0. Epub 2007 Sep 22.
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.
甲状腺激素（TH）不足会导致人类出现不同程度的听力障碍和智力缺陷。缺乏TH的啮齿动物患有先天性听力缺陷，这归因于听觉系统的生理、形态和发育异常。我们研究了四种基因定义的甲状腺功能减退小鼠品系，观察其听力发育情况以及在妊娠后期开始并持续到六周龄的TH替代治疗的反应。听觉脑干反应研究表明，在三周龄时，每个品系的纯合突变体相对于正常同窝小鼠存在不同程度的听力障碍。其中三个品系的突变体在六周龄时仍存在听力缺陷。富含TH的饮食相对于未治疗的突变体，显著改善了每个品系三周龄突变体的听力。Prop1df和Pit1dw突变体在相同发育途径上存在缺陷，它们之间听力障碍程度的差异被确定是由于遗传背景修饰基因所致。对Cgatm1Sac品系进行的进一步生理和形态学研究表明，听力不佳是由于耳蜗缺陷。我们得出结论，在小鼠听力发育的关键时期给予TH补充剂，可以预防与异质性遗传病因的先天性甲状腺功能减退相关的耳聋。
