Congenital hypothyroid Pax8(-/-) mutant mice can be rescued by inactivating the TRalpha gene.
Mice devoid of all TRs are viable, whereas Pax8(-/-) mice, which lack the follicular cells producing T4 and T3 in the thyroid gland, die during the first weeks of postnatal life. A precise comparison between the two types of mutants reveals that their phenotypes are similar, but the defects in spleen, bone, and small intestine are more pronounced in Pax8(-/-) mice. This is interpreted as the result of a negative effect of the unliganded TR on thyroid hormone target genes expression in the Pax8(-/-) mutants. Pax8/TRalpha compound mutants can survive to adulthood, and the expression of target genes is partially restored. This demonstrates the importance of TRalpha aporeceptor activity in several aspects of postnatal development.
Flamant
Frédéric
F
Laboratoire de Biologie Moléculaire et Cellulaire de l'Ecole Normale Supérieure de Lyon, Unité Mixte de Recherche Centre National de la Recherche Scientifique 5665 LA INRA913, 69364 Lyon Cedex 07, France. Frederic.Flamant@ens-lyon.fr
Poguet
Anne-Lise
AL
Plateroti
Michelina
M
Chassande
Olivier
O
Gauthier
Karine
K
Streichenberger
Nathalie
N
Mansouri
Ahmed
A
Samarut
Jacques
J
D000818:Animals; D003409:Congenital Hypothyroidism; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D020868:Gene Silencing; D006720:Homozygote; D007037:Hypothyroidism / Q000235:genetics* / Q000503:physiopathology*; D051379:Mice; D008817:Mice, Mutant Strains; D009687:Nuclear Proteins; D000072636:PAX8 Transcription Factor; D051761:Paired Box Transcription Factors; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics* / Q000378:metabolism; D011988:Receptors, Thyroid Hormone; D013154:Spleen / Q000473:pathology; D015996:Survival Rate; D013961:Thyroid Gland / Q000503:physiopathology; D013972:Thyrotropin / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism; D014284:Triiodothyronine / Q000378:metabolism
D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D000072636:PAX8 Transcription Factor; D051761:Paired Box Transcription Factors; C499496:Pax8 protein, mouse; D018160:Receptors, Cytoplasmic and Nuclear; D011988:Receptors, Thyroid Hormone; D015534:Trans-Activators; D014284:Triiodothyronine; D013972:Thyrotropin