PuSH - Publication Server of Helmholtz Zentrum München: Validation of <em>Mct8/Oatp1c1</em> dKO mice as a model organism for the Allan-Herndon-Dudley Syndrome.

Navigation

Home

Deutsch

Research

Advanced Search

Browse by ...

... Journal

... Publication Type

... Research Data

... Publication Year

Publication overview

Support & Contact

Contact persons

Help

Data protection

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)

Publ. Version/Full Text

Research data

DOI

PMC

	Open Access Gold

Abstract
Metrics
Extra information

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.

Altmetric

Additional Metrics?

[➜Log in]

Edit extra informations Login

Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Allan-herndon Dudley Syndrome ; Energy Metabolism ; Mct8 ; Motor Coordination ; Myelination ; Oatp1c1 ; Thyroid Hormone

ISSN (print) / ISBN 2212-8778

e-ISSN 2212-8778

Journal Molecular Metabolism

Quellenangaben Volume: 66, Article Number: 101616

Publisher Elsevier

Publishing Place Amsterdam

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) 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)

Grants Bundesministerium für Bildung und Forschung
Deutsche Forschungsgemeinschaft
European Research Council
German Center for Diabetes Research
European Research Council ERC-CoG