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Molenaar, A. ; Mallet, N. ; Bralo, M. ; Höher, L. ; Schriever, S.C. ; Pathak, E. ; Bernecker, M. ; Müller, T.D. ; Ertürk, A. ; Cebrian Serrano, A. ; Pfluger, P.T.

A novel tamoxifen-inducible Mct8-CreERT2 mouse model for targeted studies of Mct8-expressing cells and thyroid hormone transport and function.

Transgenic Res. 34:50 (2025)
DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
Deficiency of the Monocarboxylate Transporter 8 (MCT8) severely impairs thyroid hormone (TH) transport into the brain, disrupting brain development as well as peripheral TH homeostasis. Studies assessing MCT8 expression patterns and tissue-specific pathologies induced by local TH-deficiency are often inconclusive due to unreliable antibody staining and the lack of functional tools to specifically target MCT8-expressing cells. For this purpose, we generated non-inducible Mct8-Cre and tamoxifen-inducible Mct8-CreERT2 mice. Mct8-Cre;Sun1-sfGFP mice demonstrated ubiquitous Sun1-sfGFP expression, due to early recombination driven by Mct8 gene expression at the stage of trophoblast implantation. Tamoxifen injection in 6-week-old Mct8-CreERT2 mice induced reporter expression specifically in Mct8-expressing cells in the brain and peripherally in liver, kidney, and thyroid, without leaky reporter expression in vehicle controls. Using vDISCO tissue clearing and 3D-imaging of GFP-nanobody-boosted mice, we further identified the sublingual salivary gland and the prostate as prominent Mct8-expressing organs. Nuclei from Mct8-expressing cells in the brain could selectively be enriched using fluorescence-activated nuclei sorting on Mct8-CreERT2;Sun1-sfGFP mice and characterized as choroid plexus cells and tanycytes. Our new inducible Mct8-CreERT2 line provides researchers with a tool to reliably mark, enrich, and characterize Mct8-expressing cells and to genetically modify genes specifically in these cells to study thyroid hormone transport and function.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Choroid Plexus ; Cre ; Mct8 ; Tanycyte ; Thyroid Hormone; Mice Deficient; Mct8; Expression; Fertility; Mutations; Saliva; Cre
ISSN (print) / ISBN 0962-8819
e-ISSN 1573-9368
Journal Transgenic Research
Quellenangaben Volume: 34, Issue: 1, Pages: , Article Number: 50 Supplement: ,
Publisher Springer
Publishing Place Van Godewijckstraat 30, 3311 Gz Dordrecht, Netherlands
Reviewing status Peer reviewed
Institute(s) Institute of Diabetes and Obesity (IDO)
Institute for Intelligent Biotechnologies (IBIO)
Grants
European Research Council
Deutsche Forschungsgemeinschaft
Helmholtz Zentrum Mnchen - Deutsches Forschungszentrum fr Gesundheit und Umwelt (GmbH) (4209)