Genetic determinants of susceptibility to excitotoxic cell death: Implications for gene targeting approaches
Genetic determinants of susceptibility to excitotoxic cell death: Implications for gene targeting approaches
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DOI：
10.1073/pnas.94.8.4103
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发表时间：
1997-04-15
影响因子：
11.1
通讯作者：
Steward, O
中科院分区：
文献类型：
--
作者：
Schauwecker, PE;Steward, O
最近的研究试图确定参与兴奋性神经变性的基因。在这里，我们报告说，某些品系的小鼠，包括用于基因靶向研究的品系，在红藻氨酸癫痫发作后没有表现出兴奋性毒性细胞死亡。红藻氨酸在129/SvEMS和FVB/N小鼠海马CA 3和CA 1亚区产生兴奋性毒性细胞死亡，其模式与大鼠相同。C57 BL/6和BALB/c小鼠仅在非常高剂量的红藻氨酸盐下表现出兴奋性毒性细胞死亡，并且仅在非常有限的区域中表现出兴奋性毒性细胞死亡，尽管它们表现出相当的癫痫发作。使用来自129/SvEMS小鼠的胚胎干细胞产生的129/SvEMS x C57 BL/6小鼠的杂交体也没有表现出兴奋性毒性细胞死亡。这些结果表明，C57 BL/6和BALB/c菌株携带传递保护免受谷氨酸诱导的兴奋性毒性的基因。这种对兴奋性毒性的不同易感性代表了基因靶向研究的潜在并发症。
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.