Peroxiredoxin 6 deficiency and atherosclerosis susceptibility in mice:: significance of genetic background for assessing atherosclerosis
Peroxiredoxin 6 deficiency and atherosclerosis susceptibility in mice:: significance of genetic background for assessing atherosclerosis
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DOI：
10.1016/j.atherosclerosis.2004.06.007
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发表时间：
2004-11-01
期刊：
影响因子：
5.3
通讯作者：
Paigen, B
中科院分区：
文献类型：
--
作者：
Wang, XS;Phelan, SA;Paigen, B
过氧化物氧还蛋白6（Prdx 6;也称为抗氧化蛋白2或Aop 2）是Ath 1的候选基因，Ath 1是负责小鼠品系C57 BL/6 J（136）和C3 H/HeJ（C3 H）对饮食诱导的动脉粥样硬化的各自易感性和抗性的基因座。为了评估Prdx 6是否是Ath 1的基础，我们比较了不同遗传背景的Prdx 6靶向突变（Prdx 6（-/-））小鼠中饮食诱导的动脉粥样硬化病变：136，129和B6;129。PRDX 6蛋白和mRNA在正常和动脉粥样硬化动脉中均有表达。B6;129 Prdx 6（-/-）巨噬细胞氧化LDL显著高于对照组。血浆脂质过氧化氢水平较高的致动脉粥样硬化饮食喂养Prdx 6（-/-）小鼠与B6; 129和136背景比对照组。在129遗传背景中，Prdx 6（-/-）和对照具有相同的病变抗性，而在136遗传背景中，Prdx 6（-/-）和对照具有相同的病变易感性。相比之下，136; 129背景中的Prdx 6（-/-）小鼠具有比同窝野生型对照显著更大的主动脉根部病变。因此，尽管PRDX 6蛋白在抗性129背景或易感性136背景中不影响动脉粥样硬化易感性，但在具有促动脉粥样硬化基因和抗动脉粥样硬化基因混合的背景中，它可能抑制动脉粥样硬化。因此，遗传背景在调节靶向突变小鼠的动脉粥样硬化形成中起重要作用。然而，我们认为Prdx 6不太可能是Ath 1的基础。(C)2004爱思唯尔爱尔兰有限公司保留所有权利。
Peroxiredoxin 6 (Prdx6; also called antioxidant protein 2, or Aop2) is a candidate gene for Ath1, a locus responsible for the respective susceptibility and resistance of mouse strains C57BL/6J (136) and C3H/HeJ (C3H) to diet-induced atherosclerosis. To evaluate if Prdx6 underlies Ath1, we compared the diet-induced atherosclerotic lesions in Prdx6 targeted mutant (Prdx6(-/-)) mice of different genetic backgrounds: 136, 129, and B6;129. PRDX6 protein and mRNA were expressed in normal and atherosclerotic aortas. B6;129 Prdx6(-/-) macrophages oxidized LDL significantly more than did controls. Plasma lipid hydroperoxide levels were higher in atherogenic diet-fed Prdx6(-/-) mice with B6; 129 and 136 backgrounds than in controls. Prdx6(-/-) and controls in a 129 genetic background were equally lesion-resistant, and Prdx6(-/-) and controls in a 136 background were equally lesion-susceptible. In contrast, Prdx6(-/-) mice in a 136; 129 background had significantly larger aortic root lesions than did littermate wild type controls. Therefore, although PRDX6 protein did not affect atherosclerosis susceptibility in either the resistant 129 background or the susceptible 136 background, it may inhibit atherosclerosis in backgrounds with mixed pro- and anti-atherogenic genes. Thus, genetic background plays an important role in modulating atherogenesis in targeted mutant mice. However, we think it is unlikely that Prdx6 underlies Ath1. (C) 2004 Elsevier Ireland Ltd. All rights reserved.