title: 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.
authors.affiliation: Mina & Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan 52900, Israel.
authors.forename: Gad David
authors.initials: GD
authors.lastname: Vatine
authors.forename: David
authors.initials: D
authors.lastname: Zada
authors.forename: Tali
authors.initials: T
authors.lastname: Lerer-Goldshtein
authors.forename: Adi
authors.initials: A
authors.lastname: Tovin
authors.forename: Guy
authors.initials: G
authors.lastname: Malkinson
authors.forename: Karina
authors.initials: K
authors.lastname: Yaniv
authors.forename: Lior
authors.initials: L
authors.lastname: Appelbaum
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D004195:Disease Models, Animal; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D026901:Membrane Transport Proteins / Q000235:genetics; D038901:X-Linked Intellectual Disability / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D008957:Models, Genetic; D027501:Monocarboxylic Acid Transporters / Q000378:metabolism; D009123:Muscle Hypotonia / Q000235:genetics*; D009133:Muscular Atrophy / Q000235:genetics*; D009154:Mutation; D009474:Neurons / Q000473:pathology; D010641:Phenotype; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D013116:Spinal Cord / Q000378:metabolism; D027981:Symporters; D013961:Thyroid Gland / Q000378:metabolism; D013963:Thyroid Hormones / Q000378:metabolism; D015027:Zebrafish
chemical_list: D026901:Membrane Transport Proteins; D027501:Monocarboxylic Acid Transporters; D012333:RNA, Messenger; C484257:Slc16a2 protein, mouse; C570017:Slc16a2 protein, zebrafish; D027981:Symporters; D013963:Thyroid Hormones