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基因改变的过氧化物还原酶6的小鼠模型

Mouse Models of Genetically Altered Peroxiredoxin 6.

作者信息

Feinstein Sheldon I

机构信息

Institute for Environmental Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.

Peroxitech, Ltd., Philadelphia, PA 19104, USA.

出版信息

Antioxidants (Basel). 2019 Mar 27;8(4):77. doi: 10.3390/antiox8040077.

Abstract

Peroxiredoxin 6 (Prdx6) has been shown to have three enzymatic activities: peroxidase, phospholipase A₂ (PLA₂) and acyl transferase. The peroxidase activity is unusual, as it is capable of reducing phospholipid hydroperoxides (as well as hydrogen peroxide and short chain organic peroxides). Knockout and overexpressing mice have been produced that demonstrate the effect that eliminating or overproducing Prdx6 has on the animals' physiology. In addition, mutations in various amino acids of Prdx6 have been identified that interfere with different enzymatic functions as well as protein transport. These mutations were originally characterized biochemically; subsequently, several knock-in mouse strains have been produced, each containing one mutation. These mice include the S32T knock-in that affects protein transport, the C47S knock-in that inactivates the peroxidase enzymatic activity, the D140A knock-in that inactivates the PLA₂ enzymatic activity and the H26A knock-in that inactivates the peroxidase and blocks binding to phospholipids. This review summarizes the properties of these mice based upon studies conducted with the knockout, overexpressing and knock-in mice and the effect of the genetic changes on the biochemistry and physiology of these mice. The availability of these mice is also briefly discussed.

摘要

过氧化物酶体增殖物激活受体6(Prdx6)已被证明具有三种酶活性:过氧化物酶、磷脂酶A₂(PLA₂)和酰基转移酶。其过氧化物酶活性不同寻常,因为它能够还原磷脂氢过氧化物(以及过氧化氢和短链有机过氧化物)。已经培育出基因敲除和过表达小鼠,以证明消除或过量产生Prdx6对动物生理的影响。此外,还鉴定出Prdx6各种氨基酸的突变,这些突变会干扰不同的酶功能以及蛋白质运输。这些突变最初是通过生物化学方法进行表征的;随后,培育出了几种基因敲入小鼠品系,每个品系都含有一种突变。这些小鼠包括影响蛋白质运输的S32T基因敲入小鼠、使过氧化物酶活性失活的C47S基因敲入小鼠、使PLA₂酶活性失活的D140A基因敲入小鼠以及使过氧化物酶失活并阻止与磷脂结合的H26A基因敲入小鼠。本综述基于对基因敲除、过表达和基因敲入小鼠的研究,总结了这些小鼠的特性以及基因变化对其生物化学和生理学的影响。还简要讨论了这些小鼠的可用性。

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