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Validation of Mct8/Oatp1c1 dKO mice as a model organism for the Allan-Herndon-Dudley Syndrome
OBJECTIVE: The Allan-Herndon-Dudley syndrome (AHDS) is a severe disease caused by dysfunctional central thyroid hormone transport due to functional loss of the monocarboxylate transporter 8 (MCT8). In this study, we assessed whether mice with concomitant deletion of the thyroid hormone transporters...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9626936/ https://www.ncbi.nlm.nih.gov/pubmed/36270613 http://dx.doi.org/10.1016/j.molmet.2022.101616 |
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author | Maity-Kumar, Gandhari Ständer, Lisa DeAngelis, Meri Lee, Sooyeon Molenaar, Anna Becker, Lore Garrett, Lillian Amerie, Oana V. Hoelter, Sabine M. Wurst, Wolfgang Fuchs, Helmut Feuchtinger, Annette Gailus-Durner, Valerie Garcia-Caceres, Cristina Othman, Ahmed E. Brockmann, Caroline Schöffling, Vanessa I. Beiser, Katja Krude, Heiko Mroz, Piotr A. Hofmann, Susanna Tuckermann, Jan DiMarchi, Richard D. Hrabe de Angelis, Martin Tschöp, Matthias H. Pfluger, Paul T. Müller, Timo D. |
author_facet | Maity-Kumar, Gandhari Ständer, Lisa DeAngelis, Meri Lee, Sooyeon Molenaar, Anna Becker, Lore Garrett, Lillian Amerie, Oana V. Hoelter, Sabine M. Wurst, Wolfgang Fuchs, Helmut Feuchtinger, Annette Gailus-Durner, Valerie Garcia-Caceres, Cristina Othman, Ahmed E. Brockmann, Caroline Schöffling, Vanessa I. Beiser, Katja Krude, Heiko Mroz, Piotr A. Hofmann, Susanna Tuckermann, Jan DiMarchi, Richard D. Hrabe de Angelis, Martin Tschöp, Matthias H. Pfluger, Paul T. Müller, Timo D. |
author_sort | Maity-Kumar, Gandhari |
collection | PubMed |
description | OBJECTIVE: The Allan-Herndon-Dudley syndrome (AHDS) is a severe disease caused by dysfunctional central thyroid hormone transport due to functional loss of the monocarboxylate transporter 8 (MCT8). In this study, we assessed whether mice with concomitant deletion of the thyroid hormone transporters Mct8 and the organic anion transporting polypeptide (Oatp1c1) represent a valid preclinical model organism for the AHDS. METHODS: We generated and metabolically characterized a new CRISPR/Cas9 generated Mct8/Oatp1c1 double-knockout (dKO) mouse line for the clinical features observed in patients with AHDS. RESULTS: We show that Mct8/Oatp1c1 dKO mice mimic key hallmarks of the AHDS, including decreased life expectancy, central hypothyroidism, peripheral hyperthyroidism, impaired neuronal myelination, impaired motor abilities and enhanced peripheral thyroid hormone action in the liver, adipose tissue, skeletal muscle and bone. CONCLUSIONS: We conclude that Mct8/Oatp1c1 dKO mice are a valuable model organism for the preclinical evaluation of drugs designed to treat the AHDS. |
format | Online Article Text |
id | pubmed-9626936 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-96269362022-11-03 Validation of Mct8/Oatp1c1 dKO mice as a model organism for the Allan-Herndon-Dudley Syndrome Maity-Kumar, Gandhari Ständer, Lisa DeAngelis, Meri Lee, Sooyeon Molenaar, Anna Becker, Lore Garrett, Lillian Amerie, Oana V. Hoelter, Sabine M. Wurst, Wolfgang Fuchs, Helmut Feuchtinger, Annette Gailus-Durner, Valerie Garcia-Caceres, Cristina Othman, Ahmed E. Brockmann, Caroline Schöffling, Vanessa I. Beiser, Katja Krude, Heiko Mroz, Piotr A. Hofmann, Susanna Tuckermann, Jan DiMarchi, Richard D. Hrabe de Angelis, Martin Tschöp, Matthias H. Pfluger, Paul T. Müller, Timo D. Mol Metab Original Article OBJECTIVE: The Allan-Herndon-Dudley syndrome (AHDS) is a severe disease caused by dysfunctional central thyroid hormone transport due to functional loss of the monocarboxylate transporter 8 (MCT8). In this study, we assessed whether mice with concomitant deletion of the thyroid hormone transporters Mct8 and the organic anion transporting polypeptide (Oatp1c1) represent a valid preclinical model organism for the AHDS. METHODS: We generated and metabolically characterized a new CRISPR/Cas9 generated Mct8/Oatp1c1 double-knockout (dKO) mouse line for the clinical features observed in patients with AHDS. RESULTS: We show that Mct8/Oatp1c1 dKO mice mimic key hallmarks of the AHDS, including decreased life expectancy, central hypothyroidism, peripheral hyperthyroidism, impaired neuronal myelination, impaired motor abilities and enhanced peripheral thyroid hormone action in the liver, adipose tissue, skeletal muscle and bone. CONCLUSIONS: We conclude that Mct8/Oatp1c1 dKO mice are a valuable model organism for the preclinical evaluation of drugs designed to treat the AHDS. Elsevier 2022-10-18 /pmc/articles/PMC9626936/ /pubmed/36270613 http://dx.doi.org/10.1016/j.molmet.2022.101616 Text en © 2022 The Author(s) https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Original Article Maity-Kumar, Gandhari Ständer, Lisa DeAngelis, Meri Lee, Sooyeon Molenaar, Anna Becker, Lore Garrett, Lillian Amerie, Oana V. Hoelter, Sabine M. Wurst, Wolfgang Fuchs, Helmut Feuchtinger, Annette Gailus-Durner, Valerie Garcia-Caceres, Cristina Othman, Ahmed E. Brockmann, Caroline Schöffling, Vanessa I. Beiser, Katja Krude, Heiko Mroz, Piotr A. Hofmann, Susanna Tuckermann, Jan DiMarchi, Richard D. Hrabe de Angelis, Martin Tschöp, Matthias H. Pfluger, Paul T. Müller, Timo D. Validation of Mct8/Oatp1c1 dKO mice as a model organism for the Allan-Herndon-Dudley Syndrome |
title | Validation of Mct8/Oatp1c1 dKO mice as a model organism for the Allan-Herndon-Dudley Syndrome |
title_full | Validation of Mct8/Oatp1c1 dKO mice as a model organism for the Allan-Herndon-Dudley Syndrome |
title_fullStr | Validation of Mct8/Oatp1c1 dKO mice as a model organism for the Allan-Herndon-Dudley Syndrome |
title_full_unstemmed | Validation of Mct8/Oatp1c1 dKO mice as a model organism for the Allan-Herndon-Dudley Syndrome |
title_short | Validation of Mct8/Oatp1c1 dKO mice as a model organism for the Allan-Herndon-Dudley Syndrome |
title_sort | validation of mct8/oatp1c1 dko mice as a model organism for the allan-herndon-dudley syndrome |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9626936/ https://www.ncbi.nlm.nih.gov/pubmed/36270613 http://dx.doi.org/10.1016/j.molmet.2022.101616 |
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