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Maity-Kumar, G. ; Ständer, L. ; de Angelis, M. ; Lee, S.* ; Molenaar, A. ; Becker, L. ; Garrett, L. ; Amarie, O.V. ; Hölter, S.M. ; Wurst, W.* ; Fuchs, H. ; Feuchtinger, A. ; Gailus-Durner, V. ; García-Cáceres, C. ; Othman, A.E.* ; Brockmann, C.* ; Schöffling, V.I.* ; Beiser, K.* ; Krude, H.* ; Mroz, P.A.* ; Hofmann, S.M. ; Tuckermann, J.* ; DiMarchi, R.D.* ; Hrabě de Angelis, M. ; Tschöp, M.H. ; Pfluger, P.T. ; Müller, T.D.

Validation of Mct8/Oatp1c1 dKO mice as a model organism for the Allan-Herndon-Dudley Syndrome.

Mol. Metab. 66:101616 (2022)
Verlagsversion Forschungsdaten DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Allan-herndon Dudley Syndrome ; Energy Metabolism ; Mct8 ; Motor Coordination ; Myelination ; Oatp1c1 ; Thyroid Hormone
ISSN (print) / ISBN 2212-8778
e-ISSN 2212-8778
Zeitschrift Molecular Metabolism
Quellenangaben Band: 66, Heft: , Seiten: , Artikelnummer: 101616 Supplement: ,
Verlag Elsevier
Verlagsort Amsterdam
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Diabetes and Obesity (IDO)
Institute of Experimental Genetics (IEG)
Institute of Developmental Genetics (IDG)
CF Pathology & Tissue Analytics (CF-PTA)
Institute of Diabetes and Regeneration Research (IDR)
Research Unit Analytical Pathology (AAP)
Förderungen Bundesministerium für Bildung und Forschung
Deutsche Forschungsgemeinschaft
European Research Council
German Center for Diabetes Research
European Research Council ERC-CoG