huANGPTL4(1) Mouse

Angiopoietin-like protein 4 (ANGPTL4) is a member of the angiopoietin-like protein family and is highly expressed in metabolically active organs and tissues, such as the liver, adipose tissue, and small intestine ^[1]. As a physiological inhibitor of lipoprotein lipase (LPL), ANGPTL4 non-covalently binds to and inhibits LPL activity primarily through its N-terminal domain, thereby blocking the peripheral hydrolysis and clearance of triglyceride-rich lipoproteins (e.g., chylomicrons and very-low-density lipoprotein remnants) and participating in the regulation of systemic lipid metabolism and triglyceride homeostasis ^[2]. Studies have demonstrated that the dysfunction of ANGPTL4 is closely associated with obesity, type 2 diabetes (T2D), hypertriglyceridemia, atherosclerotic cardiovascular disease (ASCVD), metabolic dysfunction-associated steatotic liver disease (MASLD), and microenvironmental remodeling in malignancies such as triple-negative breast cancer, making it an important drug discovery target in metabolic disorders, cardiovascular diseases, and oncology translational medicine ^[2-5].

The huANGPTL4 mouse is a humanized model developed via gene editing technology, in which the entire sequence of the endogenous mouse Angptl4 gene from the start codon to the stop codon is replaced with the corresponding genomic DNA fragment of the human ANGPTL4 gene. This model is applicable for pathological mechanism studies of lipid metabolism disorders, organ fibrosis, and related malignancies, as well as for the screening, development, and preclinical in vivo evaluation of neutralizing antibodies, small molecule inhibitors, and nucleic acid drugs targeting human ANGPTL4.