Changes in thyroid status during early development of Mct8 deficient mice

The MCT8 deficiency syndrome is an X-linked disease presenting with severe psychomotor retardation. A feature of the syndrome is a peculiar thyroid phenotype characterized by low levels of serum T4 and rT3 and high levels of serum T3. Mice models for Mct8 deficiency replicate the thyroid tests abnormalities of humans but do not manifest gross neurological phenotype. This work demonstrates for the first time that the thyroid status in Mct8 deficient mice is highly dynamic since it changes during postnatal life from birth to adulthood. Indeed, Mct8KO mice show hyperthyroxinemia at birth, followed by a short euthyroid state during the first few days of life before manifesting the classical features of Mct8 deficiency. Moreover we found that this initial hyperthyroxinemia is accompanied by altered gene expression both in cerebral cortex and in liver suggestive of hormone excess. It is conceivable that the neonatal thyroid status of Mct8 deficient mice has a role in preserving brain function.