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Effects of perinatal thyroid hormone deprivation on the growth and behaviour of newborn mice.

TitleEffects of perinatal thyroid hormone deprivation on the growth and behaviour of newborn mice.
Publication TypeJournal Article
Year of Publication1995
AuthorsWallace H, Pate A, Bishop JO
JournalJ Endocrinol
Date Published1995 May
KeywordsAnimals, Animals, Newborn, Behavior, Animal, Female, Ganciclovir, Mice, Mice, Transgenic, Pregnancy, Thyroxine

Experiments were designed to distinguish between neonatal effects due to maternal thyroxine (T4) deprivation and those due to autonomous (fetus/pup) T4 deprivation, employing mice heterozygous for the bTG-tk transgene TG66,19 which specifically directs high-level expression of herpes virus type I thymidine kinase to the thyrocytes. Heterozygous TG66.19 females were either untreated or Ganciclovir was administered to destroy their thyrocytes and so render them T4-deficient. When mated to normal males these heterozygous females are expected to produce on average 50% normal and 50% heterozygous transgenic conceptuses. Ganciclovir was administered to the dams (both untreated and Ganciclovir-pretreated) during days 14-18 of gestation. At optimum levels of in utero Ganciclovir administration the non-transgenic pups showed no discernible effect while the transgenic pups were rendered athyrocytic and completely T4-deficient. The dams pretreated with Ganciclovir are hypothyroid throughout gestation, while the dams to which Ganciclovir was administered for the first time during gestation are not expected to become hypothyroid until about the time of parturition. In this way four sets of pups were generated for purposes of comparison: hypothyroid (transgenic) and euthyroid (non-transgenic) pups born to euthyroid dams and hypothyroid and euthyroid pups born to hypothyroid (Ganciclovir-pretreated) dams. Normal growth during days 1-10 after birth was dominated by the T4 status of the dam during gestation. Growth during days 11-21 and the correct timing of eye opening and ear elevation were dominated by the autonomous T4 status of the fetus/pup. The timely development of the surface-righting reflex (relative to weight gain) was shown to require both maternal and fetus/pup T4. The development of the cliff-avoidance reflex was independent of the T4 status of both pup and dam and of pup weight. The size of the pups at birth depended primarily on a normal T4 status in the dam but surprisingly T4 deficiency in fetuses/pups partly compensated for maternal T4 deficiency. The results presented here clearly demonstrate the utility of the HSV-tk-transgene-Ganciclovir-administration protocol in studying the interplay of maternal and fetal T4 deprivation in rodents.

Alternate JournalJ. Endocrinol.
PubMed ID7616158