huAPOE2 Mouse
Product Name
huAPOE2 Mouse
Product ID
C002043
Strain Name
C57BL/6JCya-Apoeem3(hAPOEε2)/Cya
Backgroud
C57BL/6JCya
Status
When using this mouse strain in a publication, please cite “huAPOE2 Mouse (Catalog C002043) were purchased from Cyagen.”
Product Type
Age
Genotype
Sex
Quantity
Gene Name
APOE
Gene Alias
AD2, LPG, APO-E, ApoE4, LDLCQ5
NCBI ID
Chromosome
Chr 19 (Human)
MGI ID
Datasheet
Strain Description
Apolipoprotein E ε2 (APOE2) is one of the three major human APOE isoforms, characterized by the amino acid signature Cys112/Cys158. The APOE gene is primarily expressed in the liver and central nervous system, where it is synthesized by hepatocytes and astrocytes to encode a 299-amino acid glycoprotein [1]. As a key ligand for the low-density lipoprotein (LDL) receptor family, APOE plays a critical role in cholesterol and triglyceride transport, lipoprotein metabolism, neuronal membrane repair, and the maintenance of synaptic plasticity [1-2]. Compared to APOE3, APOE2 exhibits significantly reduced binding affinity for LDL receptors, which impairs lipid clearance efficiency. Under specific genetic backgrounds, the APOE2 homozygous state can lead to Familial Dysbetalipoproteinemia (Type III Hyperlipoproteinemia) [2]. Furthermore, in contrast to APOE4, APOE2 is generally considered to possess neuroprotective properties and is associated with a reduced risk of Alzheimer's disease (AD) [3].
The huAPOE2 mouse is a humanized model generated via gene editing. The exons 2-4 plus partial flanking sequences of the mouse Apoe gene were replaced with the human APOE gene sequence including exons 2-4 and some downstream sequence of 3'UTR. The point mutation p.R176C (CGC to TGC) was introduced into the human APOE exon 4. This model is suitable for studying dyslipidemia, atherosclerosis, Type III hyperlipoproteinemia, neuroinflammation, Alzheimer's disease (AD), and other APOE2-associated disorders.
Reference
Mahley RW, Rall SC Jr. Apolipoprotein E: far more than a lipid transport protein. Annu Rev Genomics Hum Genet. 2000;1:507-537.
Schneider WJ, Innerarity TL, Mahley RW. Abnormal binding of mutant apolipoprotein E to low density lipoprotein receptors of human fibroblasts associated with type III hyperlipoproteinemia. Proc Natl Acad Sci U S A. 1981 Jan;78(1):369-73.
Corder EH, Saunders AM, Strittmatter WJ, Schmechel DE, Gaskell PC Jr, Small GW, et al. Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer's disease in late onset families. Science. 1993 Aug 13;261(5123):921-3.
Strain Strategy
The exons 2-4 plus partial flanking sequences of the mouse Apoe gene were replaced with the human APOE gene sequence including exons 2-4 and some downstream sequence of 3'UTR. The point mutation p.R176C (CGC to TGC) was introduced into the human APOE exon 4.
Figure 1. Diagram of the gene editing strategy for the generation of huAPOE2 mice.
Application Area
Screening, development, and preclinical evaluation of APOE2-targeted drugs;
Research on cardiovascular diseases, such as coronary heart disease and atherosclerosis (AS);
Research on neurodegenerative diseases, such as Alzheimer's disease (AD).
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