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Publication : Involvement of T3Ralpha- and beta-receptor subtypes in mediation of T3 functions during postnatal murine intestinal development.

First Author  Plateroti M Year  1999
Journal  Gastroenterology Volume  116
Issue  6 Pages  1367-78
PubMed ID  10348820 Mgi Jnum  J:55782
Mgi Id  MGI:1339401 Doi  10.1016/s0016-5085(99)70501-9
Citation  Plateroti M, et al. (1999) Involvement of T3Ralpha- and beta-receptor subtypes in mediation of T3 functions during postnatal murine intestinal development. Gastroenterology 116(6):1367-78
abstractText  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. Methods: We used strains of knockout mice lacking T3R alpha, T3R beta, or both receptors, encoded by T3R alpha and T3R beta genes. Results: Morphological features and expression of digestive enzymes and of two intestinal regulators, Cdx-1 and Cdx-2, were compared in wildtype and T3R alpha, T3R beta, and T3R alpha beta knockout animals. T3R alpha-/- 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 T3R alpha beta double mutants. In contrast, no changes occurred in T3R beta mice. Conclusions: These data describe for the first time a direct effect of TH through the T3R alpha-receptor subtypes on postnatal intestinal mucosa maturation. They also suggest that T3R beta receptors are dispensable but can partially substitute for T3R alpha.
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