Congenital hypothyroid Pax8(-/-) mutant mice can be rescued by inactivating the TRalpha gene

Mol Endocrinol. 2002 Jan;16(1):24-32. doi: 10.1210/mend.16.1.0766.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Congenital Hypothyroidism
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism
  • Gene Expression Regulation
  • Gene Silencing
  • Homozygote
  • Hypothyroidism / genetics*
  • Hypothyroidism / physiopathology*
  • Mice
  • Mice, Mutant Strains
  • Nuclear Proteins*
  • PAX8 Transcription Factor
  • Paired Box Transcription Factors
  • Receptors, Cytoplasmic and Nuclear / genetics*
  • Receptors, Cytoplasmic and Nuclear / metabolism
  • Receptors, Thyroid Hormone*
  • Spleen / pathology
  • Survival Rate
  • Thyroid Gland / physiopathology
  • Thyrotropin / metabolism
  • Trans-Activators / genetics*
  • Trans-Activators / metabolism
  • Triiodothyronine / metabolism


  • DNA-Binding Proteins
  • Nuclear Proteins
  • PAX8 Transcription Factor
  • Paired Box Transcription Factors
  • Pax8 protein, mouse
  • Receptors, Cytoplasmic and Nuclear
  • Receptors, Thyroid Hormone
  • Trans-Activators
  • Triiodothyronine
  • Thyrotropin