title: The pathophysiological consequences of thyroid hormone transporter deficiencies: Insights from mouse models.
abstract: BACKGROUND
  As a prerequisite for thyroid hormone (TH) metabolism and action TH has to be transported into cells where TH deiodinases and receptors are located. The trans-membrane passage of TH is facilitated by TH transporters of which the monocarboxylate transporter MCT8 has been most intensively studied. Inactivating mutations in the gene encoding MCT8 are associated with a severe form of psychomotor retardation and abnormal serum TH levels (Allan-Herndon-Dudley syndrome). In order to define the underlying pathogenic mechanisms, Mct8 knockout mice have been generated and intensively studied. Most surprisingly, Mct8 ko mice do not show any neurological symptoms but fully replicate the abnormal serum thyroid state.
  
  
  METHODS
  We will summarize the findings of these mouse studies that shed light on various aspects of Mct8 deficiency and unambiguously demonstrated the pivotal role of Mct8 in mediating TH transport in various tissues. These studies have also revealed the presence of the complex interplay between different pathogenic mechanisms that contribute to the generation of the abnormal TH serum profile.
  
  
  CONCLUSIONS
  Most importantly, studies of Mct8 ko mice indicated the presence of additional TH transporters that act in concert with Mct8. Interesting candidates for such a function are the L-type amino acid transporters Lat1 and Lat2 as well as the organic anion transporting polypeptide Oatp1c1.
  
  
  CONCLUSIONS
  Overall, the analysis of Mct8 deficient mice has greatly expanded our knowledge about the (patho-) physiological function of this transporter and established a sound basis for the characterization of additional TH transporter candidates. This article is part of a Special Issue entitled Thyroid hormone signalling.
authors.affiliation: Leibniz Institute for Age Research/Fritz Lipmann Institute, Jena, Germany. hheuer@fli-leibniz.de
authors.forename: Heike
authors.initials: H
authors.lastname: Heuer
authors.forename: Theo J
authors.initials: TJ
authors.lastname: Visser
mesh_terms: D000818:Animals; D001692:Biological Transport; D006801:Humans; D026901:Membrane Transport Proteins / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D051379:Mice; D027501:Monocarboxylic Acid Transporters / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D027981:Symporters; D013963:Thyroid Hormones / Q000235:genetics / Q000378:metabolism*
chemical_list: D026901:Membrane Transport Proteins; D027501:Monocarboxylic Acid Transporters; C090735:SLC16A2 protein, human; C484257:Slc16a2 protein, mouse; D027981:Symporters; D013963:Thyroid Hormones