Congenital Hypothyroid Pax8−/− Mutant Mice Can Be Rescued by Inactivating the TRα 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/TRα compound mutants can survive to adulthood, and the expression of target genes is partially restored. This demonstrates the importance of TRα aporeceptor activity in several aspects of postnatal development.