ZFIN ID: ZDB-PUB-121205-22
Zebrafish as a model for monocarboxyl transporter 8-deficiency
Vatine, G.D., Zada, D., Lerer-Goldshtein, T., Tovin, A., Malkinson, G., Yaniv, K., and Appelbaum, L.
Date: 2013
Source: The Journal of biological chemistry   288(1): 169-180 (Journal)
Registered Authors: Appelbaum, Lior, Lerer-Goldshtein, Tali, Malkinson, Guy, Tovin, Adi, Vatine, Gad, Yaniv, Karina, Zada, David
Keywords: animal models, neurodevelopment, neuroendocrinology, thyroid hormone, transporters, Allan-Herndon-Dudley syndrome, MCT8, Slc16a2, thyroid, zebrafish
MeSH Terms:
  • Animals
  • Brain/metabolism
  • Disease Models, Animal
  • Gene Expression Regulation, Developmental*
  • Humans
  • Membrane Transport Proteins/genetics
  • Mental Retardation, X-Linked/genetics*
  • Mice
  • Mice, Knockout
  • Models, Genetic
  • Monocarboxylic Acid Transporters/metabolism
  • Muscle Hypotonia/genetics*
  • Muscular Atrophy/genetics*
  • Mutation*
  • Neurons/pathology
  • Phenotype
  • Promoter Regions, Genetic
  • RNA, Messenger/metabolism
  • Spinal Cord/metabolism
  • Thyroid Gland/metabolism
  • Thyroid Hormones/metabolism
  • Zebrafish
PubMed: 23161551 Full text @ J. Biol. Chem.

Allan Herndon Dudley syndrome (AHDS) is a severe psychomotor retardation characterized by neurological impairment and abnormal thyroid hormone (TH) levels. Mutations in the TH transporter, monocarboxylate transporter 8 (MCT8), are associated with AHDS. MCT8-knockout mice exhibit impaired TH levels; however, they lack neurological defects. Here, the zebrafish mct8 gene and promoter were isolated, and mct8 promoter-driven transgenic lines were used to show that, similar to humans, mct8 is primarily expressed in the nervous and vascular systems. Morpholino-based knockdown and rescue experiments revealed that MCT8 is strictly required for neuron development in the brain and spinal cord. This study shows that MCT8 is a crucial regulator during embryonic development and establishes the first vertebrate model for MCT8-deficiency that exhibits a neurological phenotype.