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 Axin2^{P2A‐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.

中文翻译：

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一种新型 Axin2 敲入小鼠模型，用于 WNT/CTNNB1 响应细胞的可视化和谱系追踪。

Wnt 信号转导控制所有多细胞动物的组织形态发生、维持和再生。在哺乳动物中，WNT/CTNNB1（Wnt/β-catenin）通路控制出生前后的细胞增殖和细胞命运决定。它在胚胎发育的多个阶段起着关键作用，但也控制着成体组织中的干细胞维持和体内平衡。然而，在体内监测内源性 WNT/CTNNB1 信号动力学仍然具有挑战性。在这里，我们报告了一种新的敲入小鼠品系的产生和表征，该品系兼作 WNT/CTNNB1 响应细胞的荧光报告基因和谱系追踪驱动程序。我们在通用 WNT/CTNNB1 靶基因Axin2的 3' 末端引入了一个多顺反子靶向盒. 由此产生的敲入等位基因表达了一个明亮的荧光报告基因 (3xNLS-SGFP2) 和一个用于谱系追踪的强力霉素诱导驱动程序 (rtTA3)。我们表明Axin2 ^{P2A-rtTA3-T2A-3xNLS-SGFP2}菌株在胚胎和出生后发育的不同阶段在多个解剖部位标记 WNT/CTNNB1 响应细胞。它忠实地报告了体内发生的生理 WNT/CTNNB1 信号活动的微妙和动态变化。我们希望这种小鼠品系成为想要追踪和追踪 WNT/CTNNB1 响应性干细胞在不同环境中的位置和发育命运的生物学家的有用资源。