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目的研究小鼠未编辑的谷氨酸受体2(GluR2)Q/R部位缺失RNA2的次黄嘌呤腺苷脱氨酶(ADAR2)是否引起缓慢的运动神经元死亡。方法利用Cre/loxP重组系统制作一个条件性基因敲除ADAR2小鼠品系(AR2),利用基因组PCR和反转录PCR技术,将AR2小鼠的运动神经元ADAR2基因条件性定位,观察及检测AR2小鼠、携带内源性GluR2等位基因的未编辑GluR2 Q/R小鼠(AR2res)和对照组小鼠的GluR2 Q/R部位编辑率、行为特征、电生理以及组织形态。结果 AR2小鼠GluR2 Q/R部位编辑率降低,脊髓与脑运动神经核细胞显示因ADAR2缺乏引起的运动神经元死亡,并且出现运动神经功能衰退症状,而GluR2 Q/R部位的编辑率在动眼神经核无明显减少。当失去ADAR2活性的AR2小鼠携带内源性的GluR2等位基因时,细胞和表型的变化可以被阻止。结论 ADAR2失活可以引起运动神经元α-氨基-3-羟基-5甲基-4异恶唑-丙酸受体介导的死亡,而在未编辑的GluR2 Q/R部位缺乏ADAR2可以引起运动神经元缓慢死亡。
Aim To investigate if ADAR2, an RNA2-deficient RNA / Q-part of mouse ubiquitous glutamate receptor 2 (GluR2), causes slow motor neuron death. Methods A conditional gene knockout ADAR2 mouse strain (AR2) was constructed by Cre / loxP recombination system. The ADAR2 gene of AR2 mice was genotyped by genomic PCR and reverse transcription PCR. AR2 Mouse, GluR2 Q / R site editing rate, behavioral characteristics, electrophysiology, and histomorphology of uridine-free GluR2 Q / R mice (AR2res) bearing endogenous GluR2 alleles and control mice. Results The editing rate of GluR2 Q / R site decreased in AR2 mice. Motor neuron death in spinal cord and brain motoneuron cells was induced by ADAR2 deficiency, and motoneuron degeneration symptoms occurred. However, the editing rate of GluR2 Q / R site was lower No significant reduction in the nucleus of the eye. When AR2 mice that lose ADAR2 activity carry an endogenous GluR2 allele, changes in cells and phenotype can be prevented. CONCLUSION: Inactivation of ADAR2 induces death mediated by α-amino-3-hydroxy-5-methyl-4-isoxazole-propionate receptors in motor neurons, whereas lack of ADAR2 at the unedited GluR2 Q / R site leads to motility Neurons die slowly.