Loss of Thyroid Hormone Transporters MCT8 and OATP1C1 in Mouse Oligodendroglia Cells Results in a Delayed Oligodendrocyte Maturation and Myelination.

Authors

Joshua-Joel Richter, Boyka Markova, Beyza Atalay, Anita Boelen, Dagmar Führer, Steffen Mayerl, Heike Heuer

Published in

Thyroid : official journal of the American Thyroid Association. Pages 10507256261469832. Jul 15, 2026. Epub Jul 15, 2026.

Abstract

Due to an impaired thyroid hormone (TH) transport across brain barriers, inactivation of the murine TH transporters Mct8/Oatp1c1 causes a profound TH deficiency of the CNS that greatly impacts neural development and function. Since oligodendrocyte maturation and myelination are dependent on local TH signaling, Mct8/Oatp1c1 double knockout (DKO) mice exhibit a persistent state of hypomyelination. Yet, to which extent Mct8/Oatp1c1 inactivation also affects TH transport into oligodendroglia cells has not been addressed. Here, we studied oligodendrocyte maturation and myelination in mice lacking Mct8/Oatp1c1 specifically in oligodendroglia lineage (OL) cells and compared their phenotype with that of control and DKO animals.
Conditional Mct8/Oatp1c1 mutants were crossed with mice expressing constitutively Cre-recombinase under the control of the Olig2 promoter to inactivate both transporters in OL cells (so-called OL CKO mice). Neural maturation and myelination were assessed by immunofluorescence (IF) and fluorescence in situ hybridization (FISH) studies at different postnatal time points. Oligodendrocyte precursor cells (OPCs), premyelinating, and myelinating oligodendrocytes were visualized by coimmunolabeling.
OL CKO mice exhibited normal serum TH concentrations and hypothalamic Trh transcript levels. Quantification of neuronal TH-target gene transcript levels (Rc3; Klf9; Pde10a) revealed no alterations. Abundance of myelin sheaths-related proteins Mbp and Cnp was significantly reduced in OL CKO mice at postnatal day P12 but reached normal levels at P21 and P120. Quantification of OPC, premyelinating, and myelinating oligodendrocytes disclosed a strongly reduced number of mature OL at P6 and P12, while cell numbers normalized in adult OL CKO mice.
Inactivation of murine TH transporters Mct8/Oatp1c1 in OL cells causes a delayed oligodendroglia maturation and myelination. These findings highlight a physiologically relevant function of Mct8/Oatp1c1 in developmental oligodendrogenesis and myelin formation. In contrast to the persistent myelination defect seen in central hypothyroid DKO mice, OL CKO mice exhibit only a transient oligodendrocyte differentiation impairment and transient hypomyelination. These observations indicate the presence of additional, yet unknown, TH transporters that ultimately enable cellular TH entry into oligodendroglia cells even in the absence of Mct8/Oatp1c1.

PMID:
42455311
Bibliographic data and abstract were imported from PubMed on 15 Jul 2026.

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