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| The EMBO Journal
(1999) 18, 623–631, doi:10.1093/emboj/18.3.623 |
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Different functions for the thyroid hormone receptors TR and TR in the control of thyroid hormone production and post-natal development |
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| Karine Gauthier1, 5, Olivier Chassande1, 5, Michela Plateroti1, Jean-Paul Roux2, Claude Legrand1, Bertrand Pain1, Bernard Rousset3, Roy Weiss4, Jacqueline Trouillas3 and Jacques Samarut1 |
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1 CNRS UMR 49-INRA LA 913, Ecole Normale Supérieure, 46 allée d'Italie, 69364 Lyon cedex, France 2 INSERM U403, Hopital Edouard Herriot, Lyon, France 3 INSERM U369, Faculté de Medecine, RTH Laennec, Lyon, France 4 Thyroid Unit, MC 3090, University of Chicago, Chicago IL 60637, USA 5 K.Gauthier and O.Chassande contributed equally to this work To whom correspondence should be addressed Olivier Chassande, ochassan@ens-lyon.fr Received 26 October 1998; Accepted 25 November 1998. |
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| Abstract |
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The biological activities of thyroid hormones are thought to be mediated by receptors generated by the TR and TR loci. The existence of several receptor isoforms suggests that different functions are mediated by specific isoforms and raises the possibility of functional redundancies. We have inactivated both TR and TR genes by homologous recombination in the mouse and compared the phenotypes of wild-type, and single and double mutant mice. We show by this method that the TR receptors are the most potent regulators of the production of thyroid stimulating hormone (TSH). However, in the absence of TR, the products of the TR gene can fulfill this function as, in the absence of any receptors, TSH and thyroid hormone concentrations reach very high levels. We also show that TR, in contrast to TR, is dispensable for the normal development of bone and intestine. In bone, the disruption of both TR and TR genes does not modify the maturation delay observed in TR-/- mice. In the ileum, the absence of any receptor results in a much more severe impairment than that observed in TR-/- animals. We conclude that each of the two families of proteins mediate specific functions of triiodothyronin (T3), and that redundancy is only partial and concerns a limited number of functions. |
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| Keywords: bone, intestine, knockout, thyroid hormone receptor, TSH |
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