Angiopoietin-2 (ANG2/ANGPT2), encoded by the ANGPT2 gene, is a secreted glycoprotein of the angiopoietin family predominantly expressed in vascular endothelial cells and stored in Weibel-Palade bodies for rapid release. ANGPT2 regulates vascular biology in a context-dependent manner by binding to the Tie2 tyrosine kinase receptor, playing pivotal roles in angiogenesis and vascular remodeling ^[1]. Its molecular structure includes a coiled-coil domain facilitating oligomerization and a fibrinogen-like domain critical for receptor binding. Functionally, ANGPT2 acts as a partial Tie2 receptor antagonist to Angiopoietin-1 (ANG1). Through competitive inhibition of Tie2 signaling, ANGPT2 disrupts vascular endothelial homeostasis, inducing increased vascular permeability and structural plasticity. In synergy with vascular endothelial growth factor (VEGF), ANGPT2 drives angiogenic sprouting and pathological neovascularization. Conversely, under conditions of low or absent VEGF, it mediates vascular regression ^[2-3]. ANGPT2 plays a central pathological role in vascular proliferative diseases such as tumor angiogenesis, diabetic retinopathy, and age-related macular degeneration. Endothelial cell activation and inflammatory responses mediated by ANGPT2 also contribute to the pathogenesis of inflammatory conditions, including sepsis and rheumatoid arthritis ^[4]. Therapeutic strategies targeting ANGPT2 include monoclonal antibodies (e.g., Nesvacumab) and peptide-Fc fusion proteins (e.g., Trebananib), often combined with VEGF inhibitors to enhance anti-angiogenic efficacy ^[5-6]. Current research efforts are focused on optimizing ANGPT2/VEGF dual-target inhibition strategies and developing biomarkers, aiming to improve clinical outcomes in tumors and ocular vascular diseases and validate its translational value as a therapeutic target in vascular and inflammatory diseases ^[7-8].

B6-hANG2(ANGPT2) mouse model was generated using gene editing technology to replace the entire sequence of the mouse Angpt2 gene with the human ANGPT2 gene sequence, achieving stable expression of human ANGPT2 protein. This model is suitable for studying tumorigenesis, vascular hyperproliferative diseases (e.g., diabetic retinopathy, age-related macular degeneration), autoimmune disorders, and preclinical evaluation of human ANGPT2-targeted therapeutics.