Adult Mice Lacking Mct8 and Dio2 Proteins Present Alterations in Peripheral Thyroid Hormone Levels and Severe Brain and Motor Skill Impairments

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Title: Adult Mice Lacking Mct8 and Dio2 Proteins Present Alterations in Peripheral Thyroid Hormone Levels and Severe Brain and Motor Skill Impairments
Authors: Bárez-López, Soledad | Grijota-Martínez, Carmen | Ausó-Monreal, Eva | Fernández-de Frutos, Mario | Montero-Pedrazuela, Ana | Guadaño-Ferraz, Ana
Research Group/s: Neurobiología del Sistema Visual y Terapia de Enfermedades Neurodegenerativas (NEUROVIS)
Center, Department or Service: Universidad de Alicante. Departamento de Óptica, Farmacología y Anatomía
Keywords: Mct8 deficiency | Deiodinase type 2 | Mouse model | Motor skills impairments | Histological brain impairments
Knowledge Area: Anatomía y Embriología Humana
Issue Date: 14-Nov-2019
Publisher: Mary Ann Liebert
Citation: Thyroid. 2019, 29(11). doi:10.1089/thy.2019.0068
Abstract: Background: Mutations in the thyroid hormone (TH) transporter monocarboxylate transporter 8 (MCT8) lead to peripheral hyperthyroidism and profound psychomotor alterations in humans. Mice lacking Mct8 present peripheral hyperthyroidism but no gross neurological abnormalities due to brain compensatory mechanisms involving the enzyme deiodinase type 2 (Dio2). Methods: Here we have analyzed the endocrine and neurologic phenotype of mice lacking both Mct8 and Dio2 at three and six months of age. Thyroxine (T4) and 3,5,3′ triiodothyronine (T3) levels/content were measured by specific radioimmunoassays; motor skill performance was evaluated by the footprint, rotarod, four limb hanging wire, and balance beam tests; and brain histological analysis was performed by immunostaining for neurofilament and parvalbumin. Results: We have found that this mouse model presents peripheral hyperthyroidism and brain hypothyroidism. Interestingly, the severity of the brain hypothyroidism seems permanent and varies across regions, with the striatum being a particularly affected area. We have also found brain alterations at the histological level compatible with TH deficiency and impaired motor skills. Conclusions: These findings indicate the potential of Mct8/Dio2-deficient mice to represent a model for human MCT8 deficiency, to understand the mechanisms underlying its pathophysiology, and ultimately design therapeutic interventions for human patients.
Sponsor: This work was supported by Grants from the Spanish Plan Nacional de I+D+i (grant number SAF2017-86342-R to A.GF), the Sherman Foundation (OTR02211 to A.GF and S.BL) and the Center for Biomedical Research on Rare Diseases (Ciberer), Instituto de Salud Carlos III, Madrid, Spain. The cost of this publication has been paid in part by FEDER funds.
ISSN: 1050-7256 (Print) | 1557-9077 (Online)
DOI: 10.1089/thy.2019.0068
Language: eng
Type: info:eu-repo/semantics/article
Rights: © 2019 Mary Ann Liebert, Inc.
Peer Review: si
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Appears in Collections:INV - NEUROVIS - Artículos de Revistas

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