TY - JOUR
T1 - Development of auditory brainstem responses (ABRs) in Tshr mutant mice derived from euthyroid and hypothyroid dams
AU - Sprenkle, Pamela M.
AU - McGee, JoAnn
AU - Bertoni, John M.
AU - Walsh, Edward J.
PY - 2001
Y1 - 2001
N2 - Developmental changes in auditory brainstem responses (ABRs) to clicks and tone bursts were studied in genetically hypothyroid Tshr mutant mice that were homozygous for the hypothyroid trait (hyt/hyt), as well as in euthyroid individuals that were heterozygous for the trait (+/hyt). The developmental role of maternal thyroid hormones was determined by comparing homozygotes that were offspring of euthyroid (hyt/hyt(e)) or hypothyroid (hyt/hyt(h)) dams; all heterozygotes were born to euthyroid dams (+/hyt(e)). Clear responses to high-level stimuli were recorded from heterozygotes on postnatal day 12 (P12) for most stimulus conditions, and thresholds, response amplitudes, interpeak intervals, and latencies developed normally, achieving nearly adult properties by P21. Most hyt/hyt(h) animals were unresponsive to acoustic stimulation throughout the period of study. Grossly immature responses to high-level stimuli were observed in many hyt/hyt(e) pups on P15; however, clear, low-amplitude responses were not routinely observed until P21. Thresholds improved with age in +/hyt(e) and hyt/hyt(e) individuals, and latency-level curves were relatively steep in young animals and developed normally in +/hyt(e) mice with the most significant changes occurring between P15 and P21. In general, hyt/hyt(e) mice exhibited prolonged latencies, interpeak intervals, and central conduction times throughout the age range studied, and slopes of latency-level curves remained abnormally steep through P28. Response amplitudes were generally larger in heterozygotes than in hyt/hyt(e) mice, regardless of level. Replacement of thyroxin during the first 10 postnatal days in hyt/hyt(h) pups had little to no effect on the development of auditory function, although more animals from this group were responsive at very high stimulation levels. We conclude that auditory function is impaired in hypothyroid Tshr animals throughout development and that impairment is profound when individuals are not exposed to maternal thyroid hormone, i.e., a clear thyroxin-dependent critical prenatal period exists in the Tshr mutant mouse.
AB - Developmental changes in auditory brainstem responses (ABRs) to clicks and tone bursts were studied in genetically hypothyroid Tshr mutant mice that were homozygous for the hypothyroid trait (hyt/hyt), as well as in euthyroid individuals that were heterozygous for the trait (+/hyt). The developmental role of maternal thyroid hormones was determined by comparing homozygotes that were offspring of euthyroid (hyt/hyt(e)) or hypothyroid (hyt/hyt(h)) dams; all heterozygotes were born to euthyroid dams (+/hyt(e)). Clear responses to high-level stimuli were recorded from heterozygotes on postnatal day 12 (P12) for most stimulus conditions, and thresholds, response amplitudes, interpeak intervals, and latencies developed normally, achieving nearly adult properties by P21. Most hyt/hyt(h) animals were unresponsive to acoustic stimulation throughout the period of study. Grossly immature responses to high-level stimuli were observed in many hyt/hyt(e) pups on P15; however, clear, low-amplitude responses were not routinely observed until P21. Thresholds improved with age in +/hyt(e) and hyt/hyt(e) individuals, and latency-level curves were relatively steep in young animals and developed normally in +/hyt(e) mice with the most significant changes occurring between P15 and P21. In general, hyt/hyt(e) mice exhibited prolonged latencies, interpeak intervals, and central conduction times throughout the age range studied, and slopes of latency-level curves remained abnormally steep through P28. Response amplitudes were generally larger in heterozygotes than in hyt/hyt(e) mice, regardless of level. Replacement of thyroxin during the first 10 postnatal days in hyt/hyt(h) pups had little to no effect on the development of auditory function, although more animals from this group were responsive at very high stimulation levels. We conclude that auditory function is impaired in hypothyroid Tshr animals throughout development and that impairment is profound when individuals are not exposed to maternal thyroid hormone, i.e., a clear thyroxin-dependent critical prenatal period exists in the Tshr mutant mouse.
KW - Development
KW - Hearing
KW - Hypothyroidism
KW - Thyroid hormone
KW - Thyroid stimulating hormone
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UR - http://www.scopus.com/inward/citedby.url?scp=0035689408&partnerID=8YFLogxK
U2 - 10.1007/s101620010077
DO - 10.1007/s101620010077
M3 - Article
C2 - 11833607
AN - SCOPUS:0035689408
SN - 1525-3961
VL - 2
SP - 330
EP - 347
JO - JARO - Journal of the Association for Research in Otolaryngology
JF - JARO - Journal of the Association for Research in Otolaryngology
IS - 4
ER -