Department of Molecular Life Science, Tokai University School of Medicine, Isehara, Kanagawa, Japan.
Mitochondrion. 2011 Jan;11(1):155-65. doi: 10.1016/j.mito.2010.09.006. Epub 2010 Oct 18.
We have previously demonstrated that excessive mitochondrial reactive oxygen species caused by mutations in the SDHC subunit of Complex II resulted in premature death in C. elegans and Drosophila, tumors in mouse cells and infertility in transgenic mice. We now report the generation and initial characterization of conditional transgenic mice (Tet-mev-1) using our uniquely developed Tet-On/Off system, which equilibrates transgene expression to endogenous levels. The mice experienced mitochondrial respiratory chain dysfunction that induced reactive oxygen species overproduction. The mitochondrial oxidative stress resulted in excessive apoptosis leading to low birth weight and growth retardation in the neonatal developmental phase in Tet-mev-1 mice.
我们之前已经证明，由于复合物 II 的 SDHC 亚基突变导致的线粒体活性氧过多会导致线虫和果蝇的过早死亡、小鼠细胞中的肿瘤以及转基因小鼠的不育。现在，我们使用我们独特开发的 Tet-On/Off 系统生成并初步表征了条件性转基因小鼠（Tet-mev-1），该系统使转基因表达与内源性水平平衡。这些小鼠经历了线粒体呼吸链功能障碍，导致活性氧过度产生。线粒体氧化应激导致过度凋亡，从而导致 Tet-mev-1 小鼠在新生儿发育阶段的出生体重低和生长迟缓。
