Generation and characterization of two transgenic mouse lines expressing human ApoE2 in neurons and glial cells.
Generation and characterization of two transgenic mouse lines expressing human ApoE2 in neurons and glial cells.
复制标题
在神经元和神经胶质细胞中表达人 ApoE2 的两个转基因小鼠系的生成和表征。
DOI：
10.1021/bi015971l
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发表时间：
2002
期刊：
影响因子：
2.9
通讯作者：
Zannis,VassilisI
中科院分区：
文献类型：
--
作者：
Georgopoulos,Spiros;McKee,Ann;Kan,Horng-Yuan;Zannis,VassilisI
Apolipoprotein E (apoE) isoforms are key determinants of susceptibility to late-onset Alzheimer's disease (AD). The ε4 and ε2 alleles have been associated with increased and decreased risk for AD, respectively. We have generated and characterized transgenic mice in which the human apoE2 gene is expressed under the control of the platelet-derived growth factor B-chain (PDGF-B) promoter, or the transferrin (TF) promoter. S1 nuclease analysis and immunoblotting showed that the PDGF-B apoE2 mice express apoE2 exclusively in the brain whereas the TF apoE2 mice express apoE2 in the liver and in the brain. In the TF apoE2 mouse line, apoE2 is also detected in the plasma. The PDGF-B apoE2 and the TF apoE2 transgenic mice were bred back to apoE-/-background. Immunohistochemical analysis showed that the PDGF apoE2 × apoE-/-and the TF apoE2 × apoE-/-mice express human apoE2 within the neocortex in hippocampal neurons and glial cells, respectively. ApoE-/-mice have been shown to develop age-dependent loss of synaptophysin. Immunoblotting of mouse brain extracts and immunohistochemical analysis of brain sections showed that apoE expression in both apoE2 × apoE-/-transgenic lines was associated with significant recovery of brain synaptophysin levels as compared to the levels of apoE-/-littermates of the same age. These apoE2-expressing mice, when bred back on amyloid precursor protein (APP) transgenic mice or other mouse lines featuring alterations in lipoprotein metabolism, may provide new mouse models for elucidating the role of apoE2 in lipid homeostasis in the brain and in the pathogenesis of AD.
