Yap1-flox Mouse

Yap1, or Yes-associated protein 1, is a transcriptional co-activator. Its activity is mainly regulated by the Hippo signaling pathway. It plays crucial roles in normal tissue homeostasis, regeneration, and is also involved in numerous biological processes such as cell proliferation, survival, and differentiation [3].

In immune thrombocytopenia (ITP), reduced Yap1 expression in megakaryocytes (MKs) was observed. In an ITP mouse model, decreased Yap1 led to aberrant MK distribution, reduced late MK percentage, and submaximal platelet recovery. Mechanistically, GATA-binding protein 1 binding to the Yap1 promoter upregulated Yap1, promoting MK maturation, and phosphorylated Yap1 facilitated thrombopoiesis by binding to myosin heavy chain 9 [1].

In diabetic kidney disease (DKD), bioinformatic analysis showed Yap1 inactivation and MQC dysregulation in renal tubule cells. Tubule cell-specific Yap1 deletion in diabetic mice exacerbated kidney injury, disrupting MQC, and promoting M1 macrophage infiltration. Administering the Yap1 activator XMU-MP-1 ameliorated these effects [2].

In summary, Yap1 is essential for normal physiological processes. Its dysregulation is implicated in diseases like ITP and DKD. Gene knockout or conditional knockout mouse models have been instrumental in uncovering its role in these disease conditions, highlighting its potential as a therapeutic target.