Unraveling the mechanism of the non-cell autonomous neuronal cell death in amyotroohic lateral sclerosis

我们检测了ALS模型小鼠脊髓中mRNA的表达水平。在225个表达水平发生变化的基因中，通过细胞型特异性转录组发现159个基因在小胶质细胞中大量表达。虽然SOD1Lt；G85R&GT；小鼠MMP12的表达水平增加了22.8倍，但通过SOD1Lt；G93A&GT；小鼠与MMP12KO；小鼠的交配实验，发现MMP12的表达水平并未受到影响。另一项将SOD1^&lt；G93A&GT；小鼠与小胶质细胞迁移相关的P2X4小鼠杂交的交配实验显示，只有雌性KO小鼠有延长寿命的趋势，尽管在统计学上没有显著意义。

We examined the expression level of mRNA in spinal cords of ALS mouse model. Among 225 genes which were changed in expression level, we found 159 genes were expressed abundantly in microglia by cell-type specific transcriptome. Though the expression level of matrix metalloproteinase 12(MMP12) increased by 22.8 fold in SOD1^<G85R> mice, no effect on life span was found by mating experiment crossing SOD1^<G93A> mice with MMP12 KO mice. Another mating experiment crossing SOD1^<G93A> mice with P2X4(which relates to microglial migration) KO mice showed tendency to extend life span only in female though statistically nonsignifcant.