Neuron-specific transgene expression of Bcl-XL but not Bcl-2 genes reduced lesion size after permanent middle cerebral artery occlusion in mice
Neuron-specific transgene expression of Bcl-XL but not Bcl-2 genes reduced lesion size after permanent middle cerebral artery occlusion in mice
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DOI：
10.1016/s0304-3940(99)00392-4
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发表时间：
1999-06
影响因子：
2.5
通讯作者：
C. Wiessner;P. Allegrini;Katrin Rupalla;D. Sauer;T. Oltersdorf;A. McGregor;S. Bischoff;B. Böttiger;H. Putten
中科院分区：
文献类型：
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作者：
C. Wiessner;P. Allegrini;Katrin Rupalla;D. Sauer;T. Oltersdorf;A. McGregor;S. Bischoff;B. Böttiger;H. Putten
在转基因小鼠中评估了局灶性脑缺血后的保护作用，这些转基因小鼠以神经元特异性的方式过度表达小鼠的BclXL或人的Bcl2。这两个基因都受相同的小鼠Thy-1调控序列的控制，导致在皮质神经元中的表达模式非常相似。此外，这些序列指导大脑中迟发性(即出生前后)的表达，从而将大脑发育过程中转基因表达的影响降至最低。采用磁共振成像技术观察大脑中动脉永久性闭塞后对脑梗塞体积的影响。与非转基因小鼠相比，Thy1mbCL-XL小鼠的脑梗塞面积显著减少了21%，而Thy1hbCL-2小鼠没有表现出任何减少。这些发现表明，在人类中风的小鼠模型中，与Bcl2相比，BclXLAS具有选择性保护优势。
Protective effects after focal cerebral ischemia were assessed in transgenic mice that overexpress in a neuron-specific fashion mouse Bcl-XLor human Bcl-2. Both Bcl genes were under the control of the same mouse Thy-1 regulatory sequences resulting in very similar expression patterns in cortical neurons. Furthermore, these sequences direct late-onset (i.e. around birth) expression in brain, thus minimizing effects of transgene expression during brain development. Effects on infarct volume were measured using MRI after permanent occlusion of the middle cerebral artery (MCA). When compared to their non-transgenic littermates, Thy1mbcl-XLmice showed a significant 21% reduction in infarct size whereas Thy1hbcl-2 mice did not reveal any reduction. These findings suggest a selective protective advantage of Bcl-XLas compared with Bcl-2 in this mouse model for human stroke.