Loss of Tmem106b leads to cerebellum Purkinje cell death and motor deficits

The loss of Tmem106b results in an age-dependent loss of cerebellar Purkinje cells accompanied with motor function deficits. Tmem106b deficiency also results in lysosomal enlargement in both Purkinje cells and microglia, and increased neuroinflammation including complement system activation. These data suggest that, in addition to myelination, Tmem106b also plays important role in maintaining the health and survival of cerebellar Purkinje cells during aging. We performed transcriptomic analyses of RNA from cerebellar tissues harvested from 15-month-old Tmem106b mice [3 Tmem106b+/+ (WT), and 3 Tmem106b-/- (KO), 2 males and 1 females per genotype].Tmem106b基因缺失可引发年龄依赖性的小脑浦肯野细胞（Purkinje cells）丢失，并伴随运动功能障碍。Tmem106b缺失还会导致浦肯野细胞与小胶质细胞（microglia）出现溶酶体肿大，同时引起包括补体系统激活在内的神经炎症反应增强。上述数据表明，除髓鞘形成（myelination）之外，Tmem106b在衰老过程中对维持小脑浦肯野细胞的健康与存活同样发挥关键作用。本研究对15月龄Tmem106b小鼠的小脑组织提取的RNA进行了转录组分析[每组基因型包含3只小鼠：3只Tmem106b+/+（野生型，WT）、3只Tmem106b-/-（基因敲除型，KO），每基因型含2只雄性与1只雌性个体]。