Loss of Flot2 expression in deep cerebellar nuclei neurons of mice with Niemann-Pick disease type C.

ABSTRACT: Niemann-Pick disease type C (NPC) is caused by a deficiency of the NPC1 or NPC2 gene, leading to storages of unesterified cholesterol and sphingolipids. Cerebellar ataxia is a main symptom of NPC and the deep cerebellar nuclei (DCN) is the sole signal output of the cerebellum. In this study, we explored the pathological changes in DCN neurons of Npc1 knockout mice (Npc1^-). We first demonstrated that DCN neurons of Npc1^- mice had prominent ganglioside GM2 accumulation in the late endosomes but not in the lysosomes. More importantly, Flot2 expression, a marker for the lipid rafts, was lost. Single-nucleus RNA sequencing analysis revealed a generalized reduction in gene expression in DCN neurons, though Camk1d, encoding one of th

SUBMITTER: Chen TI 

PROVIDER: S-EPMC10395362 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature