Sciatic nerve analysis in thyroid hormone transporters Mct8 and Oatp1c1 knockout mice
Objective: Mutations in the thyroid hormone (TH) transporter monocarboxylate transporter 8 (MCT8) cause Allan–Herndon–Dudley syndrome (AHDS), a severe form of psychomotor retardation with muscle hypoplasia and spastic paraplegia as key symptoms. These abnormalities have been attributed to impaired T...
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Bioscientifica
2025-02-01
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| Series: | European Thyroid Journal |
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| author | Steffen Mayerl Andrea Alcaide Martin Reinhard Bauer Heike Heuer |
| author_facet | Steffen Mayerl Andrea Alcaide Martin Reinhard Bauer Heike Heuer |
| author_sort | Steffen Mayerl |
| collection | DOAJ |
| description | Objective: Mutations in the thyroid hormone (TH) transporter monocarboxylate transporter 8 (MCT8) cause Allan–Herndon–Dudley syndrome (AHDS), a severe form of psychomotor retardation with muscle hypoplasia and spastic paraplegia as key symptoms. These abnormalities have been attributed to impaired TH transport across brain barriers and into neural cells, thereby affecting brain development and function. Likewise, Mct8/Oatp1c1 (organic anion-transporting polypeptide 1c1) double knockout (M/Odko) mice, a well-established murine AHDS model, display a strongly reduced TH passage into the brain as well as locomotor abnormalities. To which extent the peripheral nervous system is affected by combined MCT8/OATP1C1 deficiency has not been addressed. Methods: Using the sciatic nerve as a model, we studied the spatiotemporal expression of TH transporters as well as the sciatic thyroidal state, sciatic nerve myelination and function in M/Odko mice by immunofluorescence, qPCR, Western blotting and electrophysiology. Results: We detected MCT8 protein expression in sciatic nerve axons, whereas OATP1C1 expression was observed in a subset of endothelial cells early in postnatal development. The absence of MCT8 and OATP1C1 did not alter the thyroidal state of isolated nerves at P12. Moreover, electrophysiological studies did not disclose any significant alteration in sciatic nerve signal propagation parameters in adult M/Odko mice. Although Schwann cell numbers were similar, Western blot analysis showed a mild form of hypermyelination in adult M/Odko mice. Conclusions: Altogether, our data point to a largely unaffected sciatic nerve structure and function in the absence of MCT8 and OATP1C1. |
| format | Article |
| id | doaj-art-20acced8fd5c4e30a724e5d147825b1e |
| institution | Kabale University |
| issn | 2235-0802 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Bioscientifica |
| record_format | Article |
| series | European Thyroid Journal |
| spelling | doaj-art-20acced8fd5c4e30a724e5d147825b1e2025-02-09T12:04:31ZengBioscientificaEuropean Thyroid Journal2235-08022025-02-0114110.1530/ETJ-24-02481Sciatic nerve analysis in thyroid hormone transporters Mct8 and Oatp1c1 knockout miceSteffen Mayerl0Andrea Alcaide Martin1Reinhard Bauer2Heike Heuer3Department of Endocrinology, Diabetes & Metabolism, University Hospital Essen, University of Duisburg-Essen, Essen, GermanyDepartment of Endocrinology, Diabetes & Metabolism, University Hospital Essen, University of Duisburg-Essen, Essen, GermanyInstitute of Molecular Cell Biology, Jena University Hospital, Jena, GermanyDepartment of Endocrinology, Diabetes & Metabolism, University Hospital Essen, University of Duisburg-Essen, Essen, GermanyObjective: Mutations in the thyroid hormone (TH) transporter monocarboxylate transporter 8 (MCT8) cause Allan–Herndon–Dudley syndrome (AHDS), a severe form of psychomotor retardation with muscle hypoplasia and spastic paraplegia as key symptoms. These abnormalities have been attributed to impaired TH transport across brain barriers and into neural cells, thereby affecting brain development and function. Likewise, Mct8/Oatp1c1 (organic anion-transporting polypeptide 1c1) double knockout (M/Odko) mice, a well-established murine AHDS model, display a strongly reduced TH passage into the brain as well as locomotor abnormalities. To which extent the peripheral nervous system is affected by combined MCT8/OATP1C1 deficiency has not been addressed. Methods: Using the sciatic nerve as a model, we studied the spatiotemporal expression of TH transporters as well as the sciatic thyroidal state, sciatic nerve myelination and function in M/Odko mice by immunofluorescence, qPCR, Western blotting and electrophysiology. Results: We detected MCT8 protein expression in sciatic nerve axons, whereas OATP1C1 expression was observed in a subset of endothelial cells early in postnatal development. The absence of MCT8 and OATP1C1 did not alter the thyroidal state of isolated nerves at P12. Moreover, electrophysiological studies did not disclose any significant alteration in sciatic nerve signal propagation parameters in adult M/Odko mice. Although Schwann cell numbers were similar, Western blot analysis showed a mild form of hypermyelination in adult M/Odko mice. Conclusions: Altogether, our data point to a largely unaffected sciatic nerve structure and function in the absence of MCT8 and OATP1C1.https://etj.bioscientifica.com/view/journals/etj/14/1/ETJ-24-0248.xmlsciatic nervelat1lat2mct10slc16a2slco1c1t3t4 |
| spellingShingle | Steffen Mayerl Andrea Alcaide Martin Reinhard Bauer Heike Heuer Sciatic nerve analysis in thyroid hormone transporters Mct8 and Oatp1c1 knockout mice European Thyroid Journal sciatic nerve lat1 lat2 mct10 slc16a2 slco1c1 t3 t4 |
| title | Sciatic nerve analysis in thyroid hormone transporters Mct8 and Oatp1c1 knockout mice |
| title_full | Sciatic nerve analysis in thyroid hormone transporters Mct8 and Oatp1c1 knockout mice |
| title_fullStr | Sciatic nerve analysis in thyroid hormone transporters Mct8 and Oatp1c1 knockout mice |
| title_full_unstemmed | Sciatic nerve analysis in thyroid hormone transporters Mct8 and Oatp1c1 knockout mice |
| title_short | Sciatic nerve analysis in thyroid hormone transporters Mct8 and Oatp1c1 knockout mice |
| title_sort | sciatic nerve analysis in thyroid hormone transporters mct8 and oatp1c1 knockout mice |
| topic | sciatic nerve lat1 lat2 mct10 slc16a2 slco1c1 t3 t4 |
| url | https://etj.bioscientifica.com/view/journals/etj/14/1/ETJ-24-0248.xml |
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