Plateroti M, Chassande O, Fraichard A, Gauthier K, Freund J N, Samarut J, Kedinger M
INSERM Unité 381, Strasbourg, France.
Gastroenterology. 1999 Jun;116(6):1367-78. doi: 10.1016/s0016-5085(99)70501-9.
BACKGROUND & AIMS: Thyroid hormones are implicated in intestinal development. Their effects are mediated by nuclear receptors, which are transcriptional regulators activated upon binding of triiodothyronine. The aim of this study was to define the involvement of the receptor subtypes during intestinal development.
We used strains of knockout mice lacking T3Ralpha, T3Rbeta, or both receptors, encoded by T3Ralpha and T3Rbeta genes.
Morphological features and expression of digestive enzymes and of two intestinal regulators, Cdx-1 and Cdx-2, were compared in wild-type and T3Ralpha, T3Rbeta, and T3Ralphabeta knockout animals. T3Ralpha-/- mice had abnormal intestinal morphology, assessed by a decrease in the number of epithelial cells along the crypt-villus axis and a decrease in proliferating crypt cells. Expression of Cdx-1 and Cdx-2, and of the digestive enzymes, was down-regulated. These parameters can be partially reversed by T3 injection. A similar (jejunum) or more severe (ileum) phenotype was found in T3Ralphabeta double mutants. In contrast, no changes occurred in T3Rbeta mice.
These data describe for the first time a direct effect of TH through the T3Ralpha-receptor subtypes on postnatal intestinal mucosa maturation. They also suggest that T3Rbeta receptors are dispensable but can partially substitute for T3Ralpha.
甲状腺激素与肠道发育有关。其作用由核受体介导，核受体是在与三碘甲状腺原氨酸结合后被激活的转录调节因子。本研究的目的是确定受体亚型在肠道发育过程中的作用。
我们使用了缺乏由T3Rα和T3Rβ基因编码的T3Rα、T3Rβ或两种受体的基因敲除小鼠品系。
比较了野生型、T3Rα、T3Rβ和T3Rαβ基因敲除动物的形态学特征、消化酶以及两种肠道调节因子Cdx-1和Cdx-2的表达。T3Rα-/-小鼠肠道形态异常，表现为沿隐窝-绒毛轴的上皮细胞数量减少以及增殖的隐窝细胞数量减少。Cdx-1和Cdx-2以及消化酶的表达下调。这些参数可通过注射T3部分逆转。在T3Rαβ双突变体中发现了类似（空肠）或更严重（回肠）的表型。相比之下，T3Rβ小鼠未出现变化。
这些数据首次描述了甲状腺激素通过T3Rα受体亚型对出生后肠道黏膜成熟的直接作用。它们还表明T3Rβ受体是可有可无的，但可以部分替代T3Rα。
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