huAPOE2 Mouse
製品名
huAPOE2 Mouse
製品ID
C002043
系統名
C57BL/6JCya-Apoeem3(hAPOEε2)/Cya
背景情報
C57BL/6JCya
状況
このマウス系統を論文で使用する場合は、「huAPOE2 Mouse（カタログ番号C002043）はサイアジェンから購入しました。」と引用してください。
製品タイプ
年齢
遺伝子型
性別
数量
遺伝子名
遺伝子別名
AD2, LPG, APO-E, ApoE4, LDLCQ5
NCBI ID
染色体
Chr 19
MGI ID
さらに
系統詳細
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.
参考文献
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.
系統作製戦略
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.
適用分野
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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