Zebrafish as a model for monocarboxyl transporter 8-deficiency
- Authors
- Vatine, G.D., Zada, D., Lerer-Goldshtein, T., Tovin, A., Malkinson, G., Yaniv, K., and Appelbaum, L.
- ID
- ZDB-PUB-121205-22
- Date
- 2013
- Source
- The Journal of biological chemistry 288(1): 169-180 (Journal)
- Registered Authors
- Appelbaum, Lior, 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
-
- Brain/metabolism
- Neurons/pathology
- X-Linked Intellectual Disability/genetics*
- Muscle Hypotonia/genetics*
- Spinal Cord/metabolism
- Membrane Transport Proteins/genetics
- RNA, Messenger/metabolism
- Phenotype
- Muscular Atrophy/genetics*
- Zebrafish
- Mutation*
- Thyroid Hormones/metabolism
- Promoter Regions, Genetic
- Gene Expression Regulation, Developmental*
- Monocarboxylic Acid Transporters/metabolism
- Humans
- Animals
- Models, Genetic
- Thyroid Gland/metabolism
- Mice, Knockout
- Mice
- Disease Models, Animal
- 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.