兴奋性毒性细胞死亡易感性的遗传决定因素：对基因靶向方法的启示。
Genetic determinants of susceptibility to excitotoxic cell death: implications for gene targeting approaches.
作者信息
Schauwecker P E, Steward O
机构信息
Department of Neuroscience, University of Virginia Health Sciences Center, Charlottesville 22908, USA.
出版信息
Proc Natl Acad Sci U S A. 1997 Apr 15;94(8):4103-8. doi: 10.1073/pnas.94.8.4103.
Abstract
Recent studies have sought to identify the genes involved in excitotoxic neurodegeneration. Here we report that certain strains of mice, including strains that are used for gene targeting studies, do not exhibit excitotoxic cell death after kainic acid seizures. Kainic acid produced excitotoxic cell death in the CA3 and CA1 subfields of the hippocampus in 129/SvEMS and FVB/N mice, in the same pattern as described in rats. C57BL/6 and BALB/c mice exhibited excitotoxic cell death only at very high doses of kainate, and then only in a very restricted area, although they exhibited comparable seizures. Hybrids of 129/SvEMS x C57BL/6 mice created using embryonic stem cells from 129/SvEMS mice also did not exhibit excitotoxic cell death. These results demonstrate that C57BL/6 and BALB/c strains carry gene(s) that convey protection from glutamate-induced excitotoxicity. This differential susceptibility to excitotoxicity represents a potential complication for gene targeting studies.
摘要
近期的研究试图确定与兴奋性毒性神经退行性变相关的基因。在此我们报告，某些品系的小鼠，包括用于基因靶向研究的品系，在给予 kainic 酸惊厥后并不表现出兴奋性毒性细胞死亡。在 129/SvEMS 和 FVB/N 小鼠中，kainic 酸在海马体的 CA3 和 CA1 亚区引起兴奋性毒性细胞死亡，其模式与在大鼠中描述的相同。C57BL/6 和 BALB/c 小鼠仅在非常高剂量的 kainate 时才表现出兴奋性毒性细胞死亡，而且仅在非常局限的区域，尽管它们表现出相当的惊厥。使用来自 129/SvEMS 小鼠的胚胎干细胞培育的 129/SvEMS×C57BL/6 小鼠杂交后代也未表现出兴奋性毒性细胞死亡。这些结果表明，C57BL/6 和 BALB/c 品系携带能够对谷氨酸诱导的兴奋性毒性起保护作用的基因。这种对兴奋性毒性的不同易感性代表了基因靶向研究中的一个潜在复杂因素。
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