Defective thyroid ontogenesis in fetal hypothyroid (hyt/hyt) mice.
Thyroid glands of fetal hypothyroid (hyt/hyt) mice were studied to determine the effects of the mutant gene during embryogenesis. Comparisons of mutant and normal thyroids were made with respect to morphology, iodine-concentrating ability, and glandular thyroxine (T4) content at day 18 of gestation. Fetal hyt/hyt thyroid tissue was properly located, but incompletely differentiated. The mutant thyroid was characterized microscopically by small, poorly developed follicles with colloid diminished in PAS-staining properties. The mutant glands' ability to concentrate iodine was found to be only 5--16% of that exhibited by normal glands. When litters contained both mutant and normal off-spring, the differential iodine-concentrating ability allowed fetuses to be separated into two distinct, nonoverlapping populations. The distribution of fetal mice into high or low iodine-concentrating groups agreed closely with predicted frequencies for normal and mutant phenotypes. Thyroid content of T4 in mutant mice was found to be approximately equal to that found in age-matched normal controls. The poorly developed morphology and deficient iodine-concentrating ability of fetal thyroids from day 18 hyt/hyt mice indicated that the mutant gene acts during the ontogeny of this gland. Although such data are not available on human fetuses affected by thyroid dysgenesis, postnatal hyt/hyt mice display characteristics similar to those of infants born with this form of congenital primary hypothyroidism. Thus, elucidation of the site of mutant gene action in the mouse should contribute to our knowledge of disturbed fetal thyroid development and its implications in the adult mammal.
D000818:Animals; D005333:Fetus / Q000502:physiology; D005865:Gestational Age; D007037:Hypothyroidism / Q000503:physiopathology*; D007457:Iodine Radioisotopes / Q000378:metabolism; D051379:Mice / Q000196:embryology*; D008815:Mice, Inbred Strains; D008817:Mice, Mutant Strains; D013961:Thyroid Gland / Q000002:abnormalities / Q000033:anatomy & histology / Q000254:growth & development* / Q000378:metabolism; D013974:Thyroxine / Q000096:biosynthesis
D007457:Iodine Radioisotopes; D013974:Thyroxine