The APOE3 (Apolipoprotein E epsilon 3) gene represents the most prevalent isoform within the human population and is typically categorized as the functionally "neutral" or wild-type allele. Predominantly expressed in the liver and central nervous system, it is produced by hepatocytes and astrocytes to encode the 299-amino acid Apolipoprotein E glycoprotein ^[1]. This protein serves as a vital ligand for LDL receptors, facilitating the systemic transport and redistribution of cholesterol and triglycerides necessary for membrane stability and neural synaptic repair. While APOE3 generally supports healthy lipid homeostasis, the APOE4 isoform is associated with increased risk of cardiovascular pathologies like atherosclerosis, whereas APOE2 homozygosity (or rare APOE variants) can lead to familial dysbetalipoproteinemia in specific genetic contexts ^[2]. Furthermore, it serves as the baseline for assessing neurodegenerative risk, sitting between the neuroprotective effects of the APOE2 variant and the significantly increased Alzheimer's disease risk associated with APOE4 ^[3].

The huAPOE3 mouse is a humanized model constructed by using gene-editing technology to replace exons 2-4 and part of the flanking sequences of the mouse Apoe gene with the human APOE gene sequences, including exons 2, 3, 4, and some downstream sequence of 3’UTR. This model can be used for research on cardiovascular diseases, such as atherosclerosis, and neurodegenerative diseases, such as Alzheimer's disease (AD), as well as for the development of APOE3-targeted drugs.