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Zebrafish as a model for monocarboxyl transporter 8-deficiency.

ABSTRACT: 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 knock-out 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 neural 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.

SUBMITTER: Vatine GD

PROVIDER: S-EPMC3537011 | biostudies-literature | 2013 Jan

REPOSITORIES: biostudies-literature

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Zebrafish as a model for monocarboxyl transporter 8-deficiency.

Vatine Gad David GD Zada David D Lerer-Goldshtein Tali T Tovin Adi A Malkinson Guy G Yaniv Karina K Appelbaum Lior L

The Journal of biological chemistry 20121116 1

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 knock-out 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 primari ...[more]

PMID: 23161551

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