huAPOE4/huTFRC Mouse

Apolipoprotein E (APOE) is a critical apolipoprotein involved in lipoprotein-mediated lipid transport. As a core component of plasma lipoproteins, APOE facilitates the transport of lipids between organs through plasma and interstitial fluid and plays a pivotal role in the generation, conversion, and clearance of lipoproteins. In humans, the APOE gene has three major alleles (E2, E3, and E4), which are closely associated with atherosclerosis and Alzheimer’s disease (AD). The estimated global frequency of the E4 allele is approximately 14% ^[1]. The ApoE4 isoform is a major genetic risk factor for late-onset AD and exacerbates neurodegeneration. In addition, ApoE4-associated cerebrovascular damage may play a key role in the pathogenesis of AD ^[2]. Beyond AD, APOE4 also affects lipid homeostasis and is therefore associated with cardiovascular diseases ^[3].

The Transferrin receptor (TFRC) gene encodes Transferrin Receptor 1 (TFR1), a protein that is expressed at low levels in most normal cells but shows increased expression in highly proliferative cells, such as basal epidermal cells, intestinal epithelium, and certain activated immune cells. Brain capillary endothelial cells, which constitute the blood-brain barrier (BBB), also express this receptor at high levels ^[4]. TFR1 plays a critical role in maintaining iron metabolism and homeostasis by facilitating receptor-mediated endocytosis of iron-bound transferrin (Tf) via Tf cycling, thereby promoting iron uptake ^[5].

The huAPOE4/huTFRC mouse is a dual-gene humanized model obtained by crossing the huTFRC mouse (Catalog No.: C001860) with the huAPOE4 mouse (Catalog No.: C001867). This model can be utilized for the screening, pharmacodynamic evaluation, safety assessment, and mechanism of action studies of therapeutics targeting APOE and TFRC, as well as research on Alzheimer’s disease (AD) and blood-brain barrier (BBB) drug delivery, providing a preclinical research platform for developing related innovative therapies.