Transcription profiling of mouse BALB/c Npc1-/- and Npc1+/+ mutant cerebellum

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. Experiment 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，其小脑内的浦肯野细胞（Purkinje cells, PC）会发生变性。本研究针对浦肯野细胞变性早期与晚期两个时间点的BALB/c品系Npc1+/+和Npc1-/-小鼠小脑样本，开展了全基因组芯片基因表达分析。结果显示，浦肯野细胞特异性转录本整体表达丰度不足，这与浦肯野细胞丢失的表型相符；且在晚期时间点观察到小胶质细胞激活标志物水平升高。 实验整体设计：本研究共使用12只BALB/c品系Npc1小鼠，涵盖两个年龄组（出生后第21天P21、出生后第49天P49）与两种基因型（Npc1+/+和Npc1-/-），每组年龄-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，饲养环境完全一致；除1只外，其余均为雌性。实验动物未接受任何额外干预，仅在P21或P49时处死取材。