Dietary thyroid hormone replacement ameliorates hearing deficits in hypothyroid mice.
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.
Karolyi
I Jill
IJ
Department of Human Genetics, University of Michigan Medical School, Ann Arbor, Michigan 48109-0618, USA.
Dootz
Gary A
GA
Halsey
Karin
K
Beyer
Lisa
L
Probst
Frank J
FJ
Johnson
Kenneth R
KR
Parlow
Albert F
AF
Raphael
Yehoash
Y
Dolan
David F
DF
Camper
Sally A
SA
D000284:Administration, Oral; D000818:Animals; D004032:Diet; D006311:Hearing Disorders / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D018398:Homeodomain Proteins / Q000235:genetics; D020249:Hormone Replacement Therapy; D007037:Hypothyroidism / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D008954:Models, Biological; D009925:Organ of Corti / Q000033:anatomy & histology / Q000254:growth & development; D017084:Otoacoustic Emissions, Spontaneous / Q000235:genetics; D011989:Receptors, Thyrotropin / Q000235:genetics; D013974:Thyroxine / Q000097:blood; D050817:Transcription Factor Pit-1 / Q000235:genetics; D014284:Triiodothyronine / Q000008:administration & dosage* / Q000627:therapeutic use*
D018398:Homeodomain Proteins; C102134:Prophet of Pit-1 protein; D011989:Receptors, Thyrotropin; D050817:Transcription Factor Pit-1; D014284:Triiodothyronine; D013974:Thyroxine