TY  - JOUR
AU  - Maity-Kumar, Gandhari
AU  - Ständer, Lisa
AU  - DeAngelis, Meri
AU  - Lee, Sooyeon
AU  - Molenaar, Anna
AU  - Becker, Lore
AU  - Garrett, Lillian
AU  - Amerie, Oana V
AU  - Hoelter, Sabine M
AU  - Wurst, Wolfgang
AU  - Fuchs, Helmut
AU  - Feuchtinger, Annette
AU  - Gailus-Durner, Valerie
AU  - Garcia-Caceres, Cristina
AU  - Othman, Ahmed E
AU  - Brockmann, Caroline
AU  - Schöffling, Vanessa I
AU  - Beiser, Katja
AU  - Krude, Heiko
AU  - Mroz, Piotr A
AU  - Hofmann, Susanna
AU  - Tuckermann, Jan
AU  - DiMarchi, Richard D
AU  - Hrabe de Angelis, Martin
AU  - Tschöp, Matthias H
AU  - Pfluger, Paul T
AU  - Müller, Timo D
TI  - Validation of Mct8/Oatp1c1 dKO mice as a model organism for the Allan-Herndon-Dudley Syndrome.
JO  - Molecular metabolism
VL  - 66
SN  - 2212-8778
CY  - Oxford [u.a.]
PB  - Elsevier
M1  - DZNE-2022-01672
SP  - 101616
PY  - 2022
AB  - 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.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.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.We conclude that Mct8/Oatp1c1 dKO mice are a valuable model organism for the preclinical evaluation of drugs designed to treat the AHDS.
KW  - Animals
KW  - Mice
KW  - Monocarboxylic Acid Transporters: genetics
KW  - Symporters: genetics
KW  - Mental Retardation, X-Linked: genetics
KW  - Thyroid Hormones
KW  - Allan-Herndon Dudley Syndrome (Other)
KW  - Energy metabolism (Other)
KW  - Mct8 (Other)
KW  - Motor coordination (Other)
KW  - Myelination (Other)
KW  - Oatp1c1 (Other)
KW  - Thyroid hormone (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:36270613
C2  - pmc:PMC9626936
DO  - DOI:10.1016/j.molmet.2022.101616
UR  - https://pub.dzne.de/record/165526
ER  -