Thyroid-specific inactivation of KIF3A alters the TSH signaling pathway and leads to hypothyroidism

Abstract

Kinesins, including the kinesin 2/KIF3 molecular motor, play an important role in intracellular traffic and can deliver vesicles to distal axon terminal, to cilia, to non-polarized cell surface or to epithelial cell basolateral membrane, thus taking part to the establishment of cellular polarity. We report here the consequences of the kinesin 2 motor inactivation in the thyroid of 3 week-old Kif3a Δ/flox Pax8 Cre/+ mutant mice. Our results indicate first that 3 week-old Pax8 Cre/+ mice used in these experiments present minor thyroid functional defects resulting in a slight increase in circulating bioactive TSH and intracellular cAMP levels, sufficient to maintain blood T4 levels in the normal range. Second, Kif3a inactivation in thyrocytes markedly amplified the phenotype observed in Pax8 Cre/+ mice, resulting in an altered TSH signaling upstream of the second messenger cAMP and mild hypothyroidism. Finally, our results in mouse embryonic fibroblasts