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THRB is a nuclear receptor, regulating gene expression dependent on thyroid hormone (TH) binding. The same receptor mediates signaling pathway activation in the cytosol. The challenge is to distinguish which of the two mechanisms is responsible for physiological effects of TH. We established an iPSC cell line with two mutations (E125G_G126S) in the THRB DNA-binding domain, which abrogates nuclear action and, thus, allows to study signaling pathway activation exclusively. We also generated a THRB knockout cell line to abolish all THRB effects. Comparison of WT and these two cell lines allows attribution of thyroid hormone effects to the underlying mechanism. Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.

Citation

Katarzyna A Ludwik, Regina Jahn, Ann-Kathrin Schörding, Lars C Moeller, Harald Stachelscheid. Generation of THRB-GS(E125G_G126S) and THRB-KO human iPSC lines to study noncanonical thyroid hormone signalling. Stem cell research. 2024 Feb;74:103275

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PMID: 38100912

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