Severe psychomotor and metabolic damages caused by a mutant thyroid hormone receptor alpha 1 in mice: can patients with a similar mutation be found and treated?

Björn Vennström, Jens Mittag, Karin Wallis

Abstract

UNLABELLED: Individuals suffering from the resistance to thyroid hormone syndrome (RTH) have a mutation in thyroid hormone receptor (TR) beta. Surprisingly, no patient with a mutation in TRalpha1 has been found. To facilitate their identification, animal models with a RTH-like mutation in TRalpha1 have been generated. The mutations introduced into the mouse decrease affinity to ligand, resulting in a 'receptor-mediated hypothyroidism' in tissues expressing the mutant receptor: brain, heart and bone. The mice present minor perturbances in thyroid hormone homeostasis, but show major aberrancies in postnatal development, psychomotor behaviour and metabolism. These parameters are akin to those seen in endemic cretinism and untreated congenital hypothyroidism. Treatment of the mice with high doses of triiodothyronine leads to normalization or amelioration of the dysfunctions when applied at adequate developmental periods.

CONCLUSION: Our studies on mice suggest the existence of a potentially debilitating disease caused by a mutant TRalpha1, and provide insights for identification and treatment of corresponding patients.

Original languageEnglish
JournalActa Paediatrica, International Journal of Paediatrics
Volume97
Issue number12
Pages (from-to)1605-10
Number of pages6
ISSN0803-5253
DOIs
Publication statusPublished - 2008

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