Differential gene expression in BALB/c Npc1-/- and Npc1+/+ cerebellum. Mus musculus

Purkinje cells (PC) of the cerebellum degenerate in adult mice with mutations in the Niemann-Pick type C (NPC) disease 1 (Npc1) gene. We subjected BALB/c Npc1+/+ and Npc1-/- mouse cerebella from an early and a later time point of PC degeneration to a genome-wide microarray gene expression analysis. We found general underrepresentation of PC-specific transcripts, consistent with PC loss, and elevated markers of microglia activation at the later time point. Keywords: Niemann-Pick type C, Purkinje cell degeneration Overall design: 12 BALB/c Npc1 mice of the two ages P21 and P49 and the two genotypes Npc1+/+ and Npc1-/- were used, 3 replicates for each age and genotype. The animals were of the same breed and lived under identical housing conditions. All except one animal were female. The animals were not further treated, but only sacrificed at P21 or P49.

尼曼-匹克C型（Niemann-Pick type C, NPC）疾病1型（Npc1）基因突变的成年小鼠，其小脑浦肯野细胞（Purkinje cell, PC）会发生变性。本研究对处于PC变性早期和晚期两个时间点的BALB/c品系Npc1+/+及Npc1-/-小鼠的小脑组织，开展了全基因组芯片基因表达分析。研究发现，PC特异性转录本普遍存在表达丰度偏低的情况，这与PC丢失的现象一致；同时在晚期时间点观测到小胶质细胞激活标志物的表达水平升高。
关键词：尼曼-匹克C型疾病，浦肯野细胞变性
实验设计：本研究共使用12只BALB/c品系Npc1小鼠，涵盖P21、P49两个年龄阶段，以及Npc1+/+、Npc1-/-两种基因型，每个年龄-基因型组合设置3个生物学重复。所有实验动物均为同一品系，饲养条件完全一致；除1只外，其余均为雌性。实验未对动物进行额外干预，仅在P21或P49时间点处死取材。