Severe impairment of cerebellum development in mice expressing a dominant-negative mutation inactivating thyroid hormone receptor alpha1 isoform

Thyroid hormone deficiency is known to deeply affect cerebellum post-natal development. We present here a detailed analysis of the phenotype of a recently generated mouse model, expressing a dominant-negative TRα1 mutation. Although hormonal level is not affected, the cerebellum of these mice displays profound alterations in neuronal and glial differentiation, which are reminiscent of congenital hypothyroidism, indicating a predominant function of this receptor isoform in normal cerebellum development. Some of the observed effects might result from the cell autonomous action of the mutation, while others are more likely to result from a reduction in neurotrophic factor production.