huANGPTL3 Mouse

Angiopoietin-like 3 encoded by the ANGPTL3 gene is a member of the angiopoietin-like secretory growth factor family. The protein is mainly expressed in the liver and is a secreted glycoprotein related to angiopoietin structure. Mature human ANGPTL3 protein contains an N-terminal coiled-coil domain and a C-terminal fibrinogen (FBN)-like domain. The protein induces endothelial cell adhesion and migration by binding the FBN-like domain to integrin α5β3 and plays a role in regulating angiogenesis ^[1]. ANGPTL3 can directly inhibit lipoprotein lipase (LPL) and endothelial lipase (EL) which are closely related to the hydrolysis of circulating triglycerides (TG) and high-density lipoprotein cholesterol (HDL-C). It can increase the level of circulating TG without changing the secretion or uptake of very low-density lipoprotein (VLDL) or HDL ^[2]. ANGPTL3 is a key determinant of HDL levels and is positively correlated with high-density lipoprotein cholesterol (HDL-C) in plasma. Loss-of-function mutations in the ANGPTL3 gene can lead to familial combined hyperlipidemia (FCH) ^[3]. In addition, ANGPTL3 plays a crucial role in biological or pathological processes related to lipid metabolism, angiogenesis, and hematopoiesis, such as atherosclerosis, carcinogenesis, nephrotic syndrome, diabetes, and liver disease ^[4].

This strain is a mouse Angptl3 gene humanized model. The mouse Angptl3 gene is replaced with the human ANGPTL3 gene sequence by gene editing technology, which expresses the human ANGPTL3 protein while retaining the signal peptide of mouse Angptl3. This model can be used to study the pathogenesis of metabolic diseases such as atherosclerosis, diabetes, and familial combined hyperlipidemia (FCH), as well as the development and screening of ANGPTL3-targeted drugs. The homozygous huANGPTL3 mice are viable and fertile.