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@ARTICLE{MaityKumar:165526,
author = {Maity-Kumar, Gandhari and Ständer, Lisa and DeAngelis,
Meri and Lee, Sooyeon and Molenaar, Anna and Becker, Lore
and Garrett, Lillian and Amerie, Oana V and Hoelter, Sabine
M and Wurst, Wolfgang and Fuchs, Helmut and Feuchtinger,
Annette and Gailus-Durner, Valerie and Garcia-Caceres,
Cristina and Othman, Ahmed E and Brockmann, Caroline and
Schöffling, Vanessa I and Beiser, Katja and Krude, Heiko
and Mroz, Piotr A and Hofmann, Susanna and Tuckermann, Jan
and DiMarchi, Richard D and Hrabe de Angelis, Martin and
Tschöp, Matthias H and Pfluger, Paul T and Müller, Timo D},
title = {{V}alidation of {M}ct8/{O}atp1c1 d{KO} mice as a model
organism for the {A}llan-{H}erndon-{D}udley {S}yndrome.},
journal = {Molecular metabolism},
volume = {66},
issn = {2212-8778},
address = {Oxford [u.a.]},
publisher = {Elsevier},
reportid = {DZNE-2022-01672},
pages = {101616},
year = {2022},
abstract = {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.},
keywords = {Animals / Mice / Monocarboxylic Acid Transporters: genetics
/ Symporters: genetics / Mental Retardation, X-Linked:
genetics / Thyroid Hormones / Allan-Herndon Dudley Syndrome
(Other) / Energy metabolism (Other) / Mct8 (Other) / Motor
coordination (Other) / Myelination (Other) / Oatp1c1 (Other)
/ Thyroid hormone (Other)},
cin = {AG Wurst},
ddc = {610},
cid = {I:(DE-2719)1140001},
pnm = {352 - Disease Mechanisms (POF4-352)},
pid = {G:(DE-HGF)POF4-352},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:36270613},
pmc = {pmc:PMC9626936},
doi = {10.1016/j.molmet.2022.101616},
url = {https://pub.dzne.de/record/165526},
}