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

我们检测了ALS小鼠模型脊髓中mRNA的表达水平。在225个表达水平发生变化的基因中，通过细胞类型特异性转录组分析，发现159个基因在小胶质细胞中高表达。尽管SOD 1 ^小鼠的基质金属蛋白酶12（MMP 12）表达水平增加了22.8倍<G85R>，但通过SOD 1 ^小鼠与MMP 12 KO小鼠的交配实验，未发现对寿命的影响<G93A>。另一项将SOD 1 - 4<G93A>小鼠与P2 X4（与小胶质细胞迁移有关）KO小鼠杂交的交配实验显示，仅在雌性中有延长寿命的趋势，但统计学上不显著。

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.