RT Journal Article
T1 Adult mice lacking Mct8 and Dio2 proteins present alterations in peripheral thyroid hormone levels and severe brain and motor skill impairments
A1 Bárez López, Soledad
A1 Grijota Martínez, María Carmen
A1 Ausó, Eva
A1 Fernández de Frutos, Mario
A1 Montero Pedrazuela, Ana
A1 Guadaño Ferraz, Ana
AB 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.
PB Mary Ann Liebert
SN 1050-7256
YR 2019
FD 2019
LK https://hdl.handle.net/20.500.14352/93226
UL https://hdl.handle.net/20.500.14352/93226
LA eng
NO Bárez-López, Soledad, et al. «Adult Mice Lacking Mct8 and Dio2 Proteins Present Alterations in Peripheral Thyroid Hormone Levels and Severe Brain and Motor Skill Impairments». Thyroid, vol. 29, n.o 11, noviembre de 2019, pp. 1669-82. https://doi.org/10.1089/thy.2019.0068.
NO Ministerio de Ciencia e Innovación (España)
NO Sherman Foundation
NO Instituto de Salud Carlos III
DS Docta Complutense
RD 12 abr 2025