Evaluation of the rdw rats as an animal model for hereditary dwarfism and the causing factor for the dwarfism

rdw大鼠（基因符号; rdw）代表遗传性侏儒症作为一种常染色体隐性遗传性状。生长激素（GH）和催乳素（PRL）mRNA的表达较正常垂体低30-100倍。垂体特异性转录因子Pit-1不仅参与GH和PRL的基因表达，而且还参与生长激素、催乳激素和促甲状腺激素的基因表达。Pit-1 mRNA的表达在rdw大鼠和对照组之间无差异。我们将RDW侏儒症的病因集中在甲状腺功能上。与正常对照组相比，rdw大鼠血液中甲状腺激素水平降低，促甲状腺激素（TSH）水平升高。rdw大鼠血清TSH升高后，在FRTL-5细胞上的生物学活性与放射免疫法相当。为了阐明rdw侏儒症的特征，我们着重研究了rdw大鼠甲状腺的功能。我们对rdw大鼠进行了甲状腺激素补充治疗。rdw大鼠从断奶（5周龄）开始，以添加0.025%甲状腺粉的大鼠饲料喂养至处死。在喂食甲状腺粉补充饲料的rdw大鼠中观察到体重显著增加。在移植甲状腺的rdw大鼠中也观察到体重的显著增加。处死时，移植组大鼠的GH和PRL mRNA表达水平与正常对照组相当。移植甲状腺的雄性rdw大鼠获得了生殖功能，与rdw/+杂合子雌性交配，可产下约50%的纯合子rdw/rdw后代。这些结果表明rdw大鼠存在原发性甲状腺功能减退症。

The rdw rat (gene symbol ; rdw) represents hereditary dwarfism inherited as an autosomal recessive trait. The rdw pituitary expressed 30-100 times less growth hormone (GH) and prolactin (PRL) mRNA than normal control. The pituitary-specific transcription factor Pit-1, which is involved not only in the gene expression of GH and PRL but in somatotroph, lactotroph and thyro-troph, was examined. No difference in mRNA expression for Pit-1 was found between rdw rats and controls. We focussed the cause of rdw dwarfism on the thyroid function. The rdw rats had reduced thyroid hormone levels and raised thyroid stimulating hormone (TSH) levels in blood compared with normal controls. The raised serum TSH in rdw rats showed equivalent biological activity in FRTL-5 cells to radioimmunoassay. To clarify the feature of rdw dwarfism, we focused the function of the thyroid gland in rdw rats. We carried out thyroid hormone supplement therapy in rdw rats. The rdw rats were fed with the rat chow added with 0.025% desiccated thyroid powder from weaning (5 weeks of age) to sacrifice time. A significant increase in body weight was noted in the rdw rats fed with the thyroid powder supplemented chow. A significant increase in body weight was also observed in the rdw rats transplanted with the thyroid gland. Equivalent expression of GH and PRL mRNA to the normal control rats was noted in the thyroid transplanted rdw at sacrifice time. The male rdw rats transplanted with the thyroid gland acquired repro-ductive function and had about 50% homozygous rdw/rdw offsprings in mating with hetrozygous rdw/+ females. These results indicate Primary hypothyroidism in the rdw rat.