huANGPTL3 Mouse

Angiopoietin‑like protein 3 (ANGPTL3) is mainly expressed in the liver and is a secreted glycoprotein structurally related to angiopoietins. The mature form of human ANGPTL3 protein contains an N‑terminal coiled‑coil domain and a C‑terminal fibrinogen‑like (FBN) domain. Through binding of its FBN‑like domain to integrin αvβ3, ANGPTL3 induces endothelial cell adhesion and migration, thereby playing a role in the regulation of angiogenesis ^[1]. In addition, ANGPTL3 can directly inhibit lipoprotein lipase (LPL) and endothelial lipase (EL), which are closely involved in the hydrolysis of circulating triglycerides (TG) and high‑density lipoprotein cholesterol (HDL‑C), respectively, thereby elevating circulating TG levels and affecting HDL levels ^[2-3]. In humans, ANGPTL3 is an important factor for HDL levels, and its plasma level is positively correlated with HDL‑C. Loss‑of‑function mutations in the ANGPTL3 gene (especially homozygous or compound heterozygous) lead to familial combined hypolipidemia (FHBL2) ^[4]. Furthermore, ANGPTL3 also plays important roles in biological and pathological processes related to lipid metabolism and angiogenesis, such as atherosclerosis, tumors, nephrotic syndrome, diabetes, and liver disease ^[3].

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.