Model mice for tissue-specific deletion of the manganese superoxide dismutase (MnSOD) gene
Model mice for tissue-specific deletion of the manganese superoxide dismutase (MnSOD) gene
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DOI：
10.1016/s0006-291x(02)00933-6
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发表时间：
2002-08-23
影响因子：
3.1
通讯作者：
Shirasawa, T
中科院分区：
文献类型：
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作者：
Ikegami, T;Suzuki, Y;Shirasawa, T
锰超氧化物歧化酶(MnSOD)是线粒体中将毒性O-2(-)转化为H_2O_2的酶。以往的报道表明，小鼠体内缺乏MnSOD会导致新生死亡。因此，不能用模型鼠来分析O-2(-)损伤在成人组织中的病理作用。为了探索成人型模型小鼠，我们设计了使用Cre-loxP系统的组织特异性MnSOD条件性基因敲除小鼠。首先，我们在鸡肌动蛋白启动子(CAG)的控制下，将表达Cre重组酶的转基因小鼠与MnSOD Flox小鼠杂交。我们证实了CAG MnSOD基因敲除小鼠完全缺乏MnSOD，并在出生时死亡，验证了Cre-loxP系统的使用。接下来，我们通过与Alb-Cre转基因小鼠杂交产生了肝脏特异的MnSOD缺陷小鼠。MnSOD活性和蛋白表达均显著下调。在肝脏特异的MnSOD基因敲除小鼠的肝脏中。然而，当没有检测到脂质过氧化等生化变化时，肝脏中没有观察到明显的形态异常，这表明MnSOD在肝脏中的生理作用比之前认为的多或不那么重要。在本研究中，我们成功地获得了组织特异性MnSOD条件性基因敲除小鼠，当与组织特异性转基因Cre小鼠杂交时，将为各种年龄相关疾病的分析提供有用的工具，如糖尿病、帕金森氏病、中风和心脏病。(C)2002年埃尔塞维尔科学公司(美国)。版权所有。
Manganese superoxide dismutase (MnSOD) is the enzyme that converts toxic O-2(-) to H2O2 in mitochondria. Previous reports showed that a deficiency of MnSOD in mice was neonatal lethal. Therefore, a model mouse was not available for the analysis of the pathological role of O-2(-) injuries in adult tissues. To explore an adult-type model mouse, we designed tissue-specific MnSOD conditional knockout mice using a Cre-loxp system. First, we crossbred MnSOD flox mice with transgenic mice expressing Cre recombinase under the control of the chicken actin promoter (CAG). We confirmed that CAG MnSOD knockout mice were completely deficient in MnSOD and died as neonates, validating the use of the Cre-loxp system. Next, we generated liver-specific MnSOD-deficient mice by crossbreeding with Alb-Cre transgenic mice. MnSOD activity and protein were both significantly downregulated. in the liver of liver-specific MnSOD knockout mice. However, no obvious morphological abnormality was observed in the liver when biochemical alterations such as lipid peroxidation were not detectable, suggesting a redundant or less important physiological role for MnSOD in the liver than previously thought. In the present study, we successfully generated tissue-specific MnSOD conditional knockout mice that would provide a useful tool for the analysis of various age-associated diseases such as diabetes mellitus, Parkinson's disease, stroke, and heart disease, when crossbred with tissue-specific transgenic Cre mice. (C) 2002 Elsevier Science (USA). All rights reserved.