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A novel Axin2 knock-in mouse model for visualization and lineage tracing of WNT/CTNNB1 responsive cells

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2020

Genesis. 2020 Sep;58(9):e23387. doi: 10.1002/dvg.23387. Epub 2020 Jul 9.

A novel Axin2 knock-in mouse model for visualization and lineage tracing of WNT/CTNNB1 responsive cells

Anoeska Agatha Alida van de Moosdijk, Yorick Bernardus Cornelis van de Grift, Saskia Madelon Ada de Man, Amber Lisanne Zeeman, Renée van Amerongen

Swammerdam Institute for Life Sciences, University of Amsterdam, Amsterdam, the Netherlands.

Service type: Knock-in mice

Abstract

Wnt signal transduction controls tissue morphogenesis, maintenance and regeneration in all multicellular animals. In mammals, the WNT/CTNNB1 (Wnt/β-catenin) pathway controls cell proliferation and cell fate decisions before and after birth. It plays a critical role at multiple stages of embryonic development, but also governs stem cell maintenance and homeostasis in adult tissues. However, it remains challenging to monitor endogenous WNT/CTNNB1 signaling dynamics in vivo. Here, we report the generation and characterization of a new knock-in mouse strain that doubles as a fluorescent reporter and lineage tracing driver for WNT/CTNNB1 responsive cells. We introduced a multi-cistronic targeting cassette at the 3' end of the universal WNT/CTNNB1 target gene Axin2. The resulting knock-in allele expresses a bright fluorescent reporter (3xNLS-SGFP2) and a doxycycline-inducible driver for lineage tracing (rtTA3). We show that the Axin2P2A-rtTA3-T2A-3xNLS-SGFP2 strain labels WNT/CTNNB1 responsive cells at multiple anatomical sites during different stages of embryonic and postnatal development. It faithfully reports the subtle and dynamic changes in physiological WNT/CTNNB1 signaling activity that occur in vivo. We expect this mouse strain to be a useful resource for biologists who want to track and trace the location and developmental fate of WNT/CTNNB1 responsive stem cells in different contexts.

Keywords: Axin2; GFP reporter mouse; beta-catenin; doxycycline-inducible lineage tracing; organoids.

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