Thyroid hormone receptors (TR) are nuclear receptors encoded by two different genes respectively TRalpha and TRbeta. Each gene produces several isoforms among which several are truncated or alternative forms which are not true receptors but might regulate the activity of the true receptors.

The TRalpha1 and TRbeta1 isotypes are widely expressed in almost all tissues but their physiological roles might be quite distinct as well as their molecular targets. To address the question of the specificity of the function of the TR isotypes and isoforms, many TR mutant mice have been created either through ubiquitous or tissue specific knock out or knock in of the respective genes.

From these studies it comes out that TRalpha1 is highly involved in developmental processes taking place at the birth and post natal periods. The development of heart, brain, bone, intestine, hematopoietic tissues is controlled by TRalpha1. In contrast TRbeta isoforms are involved in the development of central nervous system and sensory functions.In the adult both isotypes of receptors are involved in the control of metabolic functions in the liver, muscle, adipose tissues and intestine.

We will present a brief review on the various aspects of TR isotypes functions assessed by experimental genetics in the mouse and then focus on some recent data showing specific roles of TR isotypes in the control of some physiological functions and in the regulation of expression of specific target genes assessed by tissue specific knock out and knock in strategies.