Vatine, G.D., Zada, D., Lerer-Goldshtein, T., Tovin, A., Malkinson, G., Yaniv, K., and Appelbaum, L. (2013) Zebrafish as a model for monocarboxyl transporter 8-deficiency. The Journal of biological chemistry. 288(1):169-180.
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.