Transporters MCT8 and OATP1C1 maintain murine brain thyroid hormone homeostasis
The article “Transporters MCT8 and OATP1C1 maintain murine brain thyroid hormone homeostasis” was published in The Journal of Clinical Investigation (JCI), Volume 124, Issue 5, 2014. Dr. Heike Heuer, the senior author of this study, summarizes the main statements.
Patients with mutations in the thyroid hormone transporter MCT8 suffer from a severe form of psychomotor retardation in combination with abnormal thyroid hormone levels (Allan-Herndon Dudley syndrome, AHDS). Mct8 knock-out (ko) mice, however, are neurologically normal, although they fully replicate the endocrine abnormalities.
The lack of any neurological impairments in these animals might be due the presence of the T4-specific transporter Oatp1c1 expressed in the murine but not in the human blood-brain barrier (BBB). Indeed, our analysis of Mct8/Oatp1c1 double ko mice revealed a highly compromised thyroid hormone (TH) transport via the BBB and a strongly reduced brain TH content while peripheral tissues were in a thyrotoxic state. Moreover, combined Mct8/Oatp1c1 deficiency affects strongly neural differentiation and leads to severe locomotor impairments. In summary, Mct8/Oatp1c1 dko mice are a well-suited animal model for unraveling the pathogenic mechanisms of AHDS and useful for testing therapeutic interventions.