Evaluation and characterization of the hyt/hyt hypothyroid mouse. II. Abnormalities of TSH and the thyroid gland.
Evaluation and characterization of the hyt/hyt hypothyroid mouse. II. Abnormalities of TSH and the thyroid gland.
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DOI：
10.1159/000125160
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发表时间：
1989-05
影响因子：
4.1
通讯作者：
S. Stein;D. Shanklin;Ladislav Krulich;Michael G. Roth;Curtis M. Chubb;Perrie M. Adams
中科院分区：
文献类型：
--
作者：
S. Stein;D. Shanklin;Ladislav Krulich;Michael G. Roth;Curtis M. Chubb;Perrie M. Adams
hyt/hyt小鼠（BALB/cBY-hyt，C.hytRF）为研究遗传性重度原发性甲状腺功能减退症的作用提供了一个有用的模型。进行研究试图确定常染色体隐性基因hyt纯合子小鼠原发性甲状腺功能减退症的基础。这些小鼠在受孕后15天胎儿发病时患有先天性甲状腺功能减退症。在它们的一生中，hyt/hyt小鼠的血清甲状腺素（T4），三碘甲状腺原氨酸（T3）降低，减少甲状腺腔内胶体的电子显微镜和100倍的升高TSH样活性相比，hyt/+同窝出生。hyt/hyt动物的甲状腺球蛋白在大小上与正常甲状腺球蛋白相似，这与甲状腺球蛋白基因的主要结构缺陷不一致。甲状腺球蛋白被碘化。在hyt/hyt小鼠滤泡细胞中观察到粗面内质网（RER）显著、不稳定的扩张。尽管这些超微结构的结果，脉冲追逐和免疫沉淀研究与孤立的hyt/hyt和正常的甲状腺表明，正常的甲状腺球蛋白处理发生在RER和高尔基体的hyt/hyt小鼠。与hyt/+同窝仔相比，hyt/hyt甲状腺发育不全。在组织学上，与hyt/+同窝仔相比，hyt/hyt甲状腺表现出较小滤泡细胞的增加和滤泡大小的更大变异性。腺体的组织学和超微结构异常与某些先天性甲状腺功能减退伴甲状腺TSH受体不敏感的病例相似。这些发现沿着TSH显著升高、胶体和血清T3和T4降低、下丘脑-垂体-甲状腺反馈系统的功效以及先前观察到的碘摄取和甲状腺内T4降低，表明hyt/hyt小鼠中的原发性甲状腺功能减退症可能是由于甲状腺TSH反应性缺陷所致。
The hyt/hyt mouse (BALB/cBY-hyt, C.hytRF) provides a useful model for exploring the effect of inherited severe primary hypothyroidism. Studies were undertaken to try to define the basis of the primary hypothyroidism in mice homozygous for the autosomal recessive gene, hyt. These mice had congenital hypothyroidism of fetal onset after 15 days post conception. Through their lifetime, the hyt/hyt mice had reduced serum thyroxine (T4), triiodothyronine (T3), reduced thyroid gland intralumenal colloid on electron microscopy and a 100-fold elevation of TSH-like activity compared to hyt/+ littermates. Thyroglobulin made in hyt/hyt animals was similar in size to normal thyroglobulin which was inconsistent with a major structural thyroglobulin gene defect. The thyroglobulin was iodinated. Marked, erratic dilation of rough endoplasmic reticulum (RER) was noted in hyt/hyt mouse follicular cells. Despite these ultrastructural findings, pulse chase and immunoprecipitation studies with isolated hyt/hyt and normal thyroid glands indicated that normal thyroglobulin processing occurred in the RER and Golgi of the hyt/hyt mice. The hyt/hyt thyroid glands were hypoplastic compared to hyt/+ littermates. Histologically, the hyt/hyt thyroid glands demonstrated an increase in smaller follicular cells, and greater variability in follicular size compared to hyt/+ littermates. Histological and ultrastructural abnormalities in the gland were similar to those seen in certain cases of human congenital hypothyroidism with TSH receptor insensitivity of the thyroid gland. These findings along with the significant TSH elevation, the reduction in colloid and in serum T3 and T4, the efficacy of the hypothalamo-pituitary-thyroid feedback system, and previous observations of reduced iodine uptake and intrathyroidal T4, suggested that primary hypothyroidism in the hyt/hyt mouse might be due to a defect in TSH responsivity of the thyroid gland.