dc.date.accessioned | 2024-02-09T17:52:24Z | |
dc.date.available | 2024-02-09T17:52:24Z | |
dc.date.created | 2023-11-16T10:26:11Z | |
dc.date.issued | 2023 | |
dc.identifier.citation | Tse, Janson O’Keefe, Ryan Rigopolous, Angela Carli, Annalisa L. E. Waaler, Jo Krauss, Stefan Johannes Karl Ernst, Matthias Buchert, Michael . A Mouse Model for the Rapid and Binomial Assessment of Putative WNT/β-Catenin Signalling Inhibitors. Biomedicines. 2023, 11(10) | |
dc.identifier.uri | http://hdl.handle.net/10852/107770 | |
dc.description.abstract | Specific signalling thresholds of the WNT/β-catenin pathway affect embryogenesis and tissue homeostasis in the adult, with mutations in this pathway frequently occurring in cancer. Excessive WNT/β-catenin activity inhibits murine anterior development associated with embryonic lethality and accounts for the driver event in 80% of human colorectal cancers. Uncontrolled WNT/β-catenin signalling arises primarily from impairment mutation in the tumour suppressor gene APC that otherwise prevents prolonged stabilisation of β-catenin. Surprisingly, no inhibitor compounds for WNT/β-catenin signalling have reached clinical use in part owing to the lack of specific in vivo assays that discriminate between on-target activities and dose-limiting toxicities. Here, we present a simple in vivo assay with a binary outcome whereby the administration of candidate compounds to pregnant and phenotypically normal Apcflox/flox mice can rescue in utero death of Apcmin/flox mutant conceptus without subsequent post-mortem assessment of WNT/β-catenin signalling. Indeed, the phenotypic plasticity of born Apcmin/flox conceptus enables future refinement of our assay to potentially enable dosage finding and cross-compound comparisons. Thus, we show for the first time the suitability of endogenous WNT/β-catenin signalling during embryonic development to provide an unambiguous and sensitive mammalian in vivo model to assess the efficacy and bioavailability of potential WNT/β-catenin antagonists. | |
dc.language | EN | |
dc.rights | Attribution 4.0 International | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | |
dc.title | A Mouse Model for the Rapid and Binomial Assessment of Putative WNT/β-Catenin Signalling Inhibitors | |
dc.title.alternative | ENEngelskEnglishA Mouse Model for the Rapid and Binomial Assessment of Putative WNT/β-Catenin Signalling Inhibitors | |
dc.type | Journal article | |
dc.creator.author | Tse, Janson | |
dc.creator.author | O’Keefe, Ryan | |
dc.creator.author | Rigopolous, Angela | |
dc.creator.author | Carli, Annalisa L. E. | |
dc.creator.author | Waaler, Jo | |
dc.creator.author | Krauss, Stefan Johannes Karl | |
dc.creator.author | Ernst, Matthias | |
dc.creator.author | Buchert, Michael | |
cristin.unitcode | 185,51,20,10 | |
cristin.unitname | SFF - Hybrid Technology Hub | |
cristin.ispublished | true | |
cristin.fulltext | original | |
cristin.qualitycode | 1 | |
dc.identifier.cristin | 2197467 | |
dc.identifier.bibliographiccitation | info:ofi/fmt:kev:mtx:ctx&ctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Biomedicines&rft.volume=11&rft.spage=&rft.date=2023 | |
dc.identifier.jtitle | Biomedicines | |
dc.identifier.volume | 11 | |
dc.identifier.issue | 10 | |
dc.identifier.pagecount | 0 | |
dc.identifier.doi | https://doi.org/10.3390/biomedicines11102719 | |
dc.type.document | Tidsskriftartikkel | |
dc.type.peerreviewed | Peer reviewed | |
dc.source.issn | 2227-9059 | |
dc.type.version | PublishedVersion | |
cristin.articleid | 2719 | |