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. 2021 Feb 25;15:628983. doi: 10.3389/fnins.2021.628983

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Copyright © 2021 Kriska, Janeckova, Kirdajova, Honsa, Knotek, Dzamba, Kolenicova, Butenko, Vojtechova, Capek, Kozmik, Taketo, Korinek and Anderova.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Modulation of the Wnt signaling pathway in transgenic mice. (A) A simplified scheme of the canonical Wnt signaling pathway that shows by color-coding where the alterations in the cascade take place. (B–E) Schemes depicting genetic modifications present in the mouse strains used in the study. (B) The transcription of the Wnt-responsive genes in the nucleus is blocked by dominant negative T-Cell Factor 4 (dnTCF4; orange) fused to the enhanced green fluorescent protein (EGFP; light green). (C) Suppression of Wnt signaling at the membrane receptor level, due to the overexpression of a secreted Wnt inhibitor Dickkopf 1 (Dkk1; dark pink). (D) Activation of the pathway by the production of a stable variant of β-catenin. Cre-mediated excision of exon 3 (E3) removes the amino acid sequence involved in the degradation of the protein, and thus stable β-catenin aberrantly hyper-activates Wnt target genes (dark green). (E) Cre deletor mouse Rosa26-CreERT2 carries the gene encoding tamoxifen/4-hydroxytamoxifen (TAM/4OHT)-inducible Cre recombinase, fused with a mutated form of the estrogen receptor (CreERT2). APC, adenomatous polyposis coli; E2-3, exons 2-3; GSK-3β, glycogen synthase kinase 3β; LRP, low-density lipoprotein receptor-related protein; pA, polyadenylation site; PGK-Neo, neomycin resistance cassette; SA, splice acceptor site; TCF/LEF, T-Cell Factor/Lymphoid Enhancer Factor; td, tandem dimer; Wnt, Wingless/Integrated.