Dr. Heike Heuer
Tissue-specific role of the murine thyroid hormone transporters Mct8 and Mct10
Thyroid hormone (TH) actions and metabolism are intracellular events that require the transport of TH across the plasma membrane. This process is facilitated by TH transporters of which the monocarboxylate transporter 8 (MCT8) has been most intensively analyzed. In humans, inactivating mutations in the X-linked MCT8 gene are associated with a severe form of psychomotor retardation in combination with abnormal serum TH parameters.
We recently provided a detailed description of Mct8 deficient mice that despite the absence of overt neurological symptoms exhibit the same unusual TH parameters as found in patients carrying MCT8 mutations. Moreover, Mct8 ko mice exhibit a complex phenotype of tissue-specific TH excess and deprivation that impedes with the analysis of tissue-specific role of Mct8.
Here, we aim to unravel the consequences of a cell-specific inactivation of Mct8 on tissue homeostasis and on the serum TH profile by taking advantage of conditional Mct8 mouse mutants and mouse mutants expressing cre-recombinase in a cell-specific manner. We will particularly study the consequence of a cell-specific inactivation of Mct8 in the liver, thyroid gland, the kidney and the pituitary as all four tissues are greatly affected by Mct8 deficiency and are putatively involved in the generation of the abnormal serum thyroid hormone levels. We further include in our studies mouse mutants that are also deficient in the TH transporter Mct10 as preliminary analysis using conventional Mct8/Mct10 deficient mouse mutants have indicated a concerted action of both TH transporters in the kidney, liver and thyroid.
In summary, we aim to elucidate the significance of Mct8 and Mct10 in facilitating TH access to its target tissue and to further elucidate mechanisms that cause the abnormal serum thyroid parameters in Mct8 deficient mice. We hope our studies will provide an insight to ameliorate the devastating conditions of patients with MCT8 mutations.
Dr. Heike Heuer
IUF – Leibniz-Institut für umweltmedizinische Forschung gGmbH
IUF – Leibniz Research Institute for Environmental Medicine
Auf’m Hennekamp 50
Phone: +49 211 3389 210
Dr. Steffen Mayerl