huAPOE4/huTFRC Mouse
제품명
huAPOE4/huTFRC Mouse
제품 ID
C002106
품종 계통
C57BL/6J;6NCya-Apoetm6(hAPOEε4)Tfrctm2(hTFRC)/Cya
Backgroud
C57BL/6J;6NCya
상태
이 마우스 계통을 논문에서 사용할 경우, “huAPOE4/huTFRC Mouse (카탈로그 번호 C002106)은 Cyagen에서 구입하였습니다.”라고 명시해 주시기 바랍니다.
구매 가능한 제품 종류
연령
Genotype
성별
수량
유전자 별칭
AD2, LPG, APO-E, ApoE4, LDLCQ5, T9, TR, TFR, p90, CD71, TFR1, TRFR, IMD46
염색체
Chr 19, Chr 3
Datasheet
품종 계통 설명
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.
Reference
Heffernan AL, Chidgey C, Peng P, Masters CL, Roberts BR. The Neurobiology and Age-Related Prevalence of the ε4 Allele of Apolipoprotein E in Alzheimer's Disease Cohorts. J Mol Neurosci. 2016 Nov;60(3):316-324.
Liu CC, Liu CC, Kanekiyo T, Xu H, Bu G. Apolipoprotein E and Alzheimer disease: risk, mechanisms and therapy. Nat Rev Neurol. 2013 Feb;9(2):106-18. doi: 10.1038/nrneurol.2012.263. Epub 2013 Jan 8. Erratum in: Nat Rev Neurol. 2013.
Mahley RW. Apolipoprotein E: from cardiovascular disease to neurodegenerative disorders. J Mol Med (Berl). 2016 Jul;94(7):739-46.
Candelaria PV, Leoh LS, Penichet ML, Daniels-Wells TR. Antibodies Targeting the Transferrin Receptor 1 (TfR1) as Direct Anti-cancer Agents. Front Immunol. 2021 Mar 17;12:607692.
Xu W, Barrientos T, Mao L, Rockman HA, Sauve AA, Andrews NC. Lethal Cardiomyopathy in Mice Lacking Transferrin Receptor in the Heart. Cell Rep. 2015 Oct 20;13(3):533-545.
변형 전략
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).
Figure 1. Gene editing strategy of huAPOE4 mice. Exons 2-4 plus partial flanking sequences were replaced with the mutant human APOE gene sequence, including exons 2–4 and part of the downstream 3′UTR sequence. The p.C130R (TGC to CGC) mutation was introduced into the mutant human APOE gene.
Figure 2. Gene editing strategy of huTFRC mice. The mouse Tfrc endogenous extracellular domain was replaced with the human TFRC extracellular domain. The murine cytoplasmic and helical regions were kept.
응용 분야
Screening, pharmacodynamic evaluation, safety evaluation, and mechanism of action research of drugs targeting APOE and TFRC;
Research on drug delivery for Alzheimer's disease (AD) and the blood-brain barrier (BBB).
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