huAPOE4 Mouse

Apolipoprotein E (APOE) is a critical apolipoprotein involved in lipid transport mediated by lipoproteins. As a core component of plasma lipoproteins, APOE facilitates the transport of lipids through plasma and interstitial fluid between organs, and it plays a pivotal role in the generation, conversion, and clearance of lipoproteins. In humans, the APOE gene has three isoforms (E2, E3, E4) associated with atherosclerosis and Alzheimer’s disease (AD), with the E4 allele present in approximately 14% of the population ^[1]. The ApoE4 isoform is a major genetic risk factor for late-onset Alzheimer’s disease (AD), exacerbating neurodegeneration. ApoE4-associated damage to vascular systems in the brain could have a key role in AD pathogenesis ^[2]. Beyond AD, APOE4 is linked to cardiovascular diseases due to its influence on lipid homeostasis ^[3].

huAPOE4 mice are humanized models constructed through gene editing technology. Exons 2-4 plus partial flanking sequences of the mouse Apoe gene were replaced in situ with the Mutant human APOE gene sequence, including exons 2, 3, and 4 and some downstream sequence of 3’UTR. The p.C130R (TGC to CGC) was introduced into the mutant human APOE gene. This model can be used for research on the pathogenic mechanisms and treatment methods of cardiovascular diseases such as diet-induced hypercholesterolemia, atherosclerosis, and lipid metabolism. It can also be used to study the role of human APOE gene polymorphisms in Alzheimer's disease.