Use of a new model of transgenic mice to clarify the respective functions of thyroid hormone receptors in vivo.
3,5,3'-Triido-L: -thyronine (T3) exerts pleiotropic actions on development and homeostasis mostly via its nuclear receptors, TRalpha1, TRbeta1, and TRbeta2, encoded by the THRA and THRB genes. Muouse genetics data outline the contrasting functions of THRA and THRB, and suggest that these are dictated by both the respective abundance of the receptor isoforms in a given cell type and the differences in the intrinsic properties of the receptors. The diversity of consequences of either hypothyroidism or THRA/THRB mutation is astonishing, suggesting that TR controls a large number of genes and that the repertoire of target gene differs from one tissue to another. In order to distinguish between the direct and indirect actions of TH in vivo, we use the CRE/LoxP recombination system to control the expression of a mutant TRalpha1 receptor with dominant negative properties. Ubiquitous expression of this mutation in heterozygous mice recapitulates many consequences of TH deficiency, except in tissues where TRbeta is highly expressed.
Flamant
Frédéric
F
Institut de Génomique Fonctionnelle de Lyon Ecole Normale Supérieure de Lyon, Université de Lyon UMR INRA CNRS 5242, IFR128 46 allée d'Italie, 69364 Lyon CEDEX 07, France. Frederic.flamant@ens-lyon.fr
Quignodon
Laure
L
D000818:Animals; D019426:Integrases / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D023421:Models, Animal; D009154:Mutation; D011995:Recombination, Genetic; D037021:Thyroid Hormone Receptors alpha / Q000235:genetics* / Q000378:metabolism*; D037042:Thyroid Hormone Receptors beta / Q000235:genetics / Q000378:metabolism*; D014284:Triiodothyronine / Q000378:metabolism*
D037021:Thyroid Hormone Receptors alpha; D037042:Thyroid Hormone Receptors beta; D014284:Triiodothyronine; C045073:Cre recombinase; D019426:Integrases