Ontology highlight
ABSTRACT:
PROVIDER: PRJNA606815 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Niemann-Pick Type C disease is an autosomal recessive neurodegenerative disorder with abnormal lipid storage as the major cellular pathologic hallmark. Genetic analyses have identified mutations in NPC1 gene in the great majority of cases, while mutations in NPC2 account for the remainders. Yet, little is known regarding the cellular mechanisms responsible for NPC pathogenesis, especially for neurodegeneration, which is the usual cause of death. To identify critical steps that could account for the pathological manifestations of the disease in one of the most affected brain structures, we performed global gene expression analysis in the cerebellum from three-week old Npc1+/+ and Npc1-/- mice with two different microarray platforms (Agilent and Illumina). Our results provide novel molecular insight regarding the mechanisms of pathogenesis in NPC disease and reveal potential new therapeutic targets. We performed global gene expression analysis in the cerebellum from three-week old Npc1+/+ and Npc1-/- mice with two different microarray platforms (Agilent and Illumina). Differentially-expressed genes identified by both microarray platforms were then subjected to KEGG pathway analysis. Expression of genes in six pathways was significantly altered in Npc1-/- mice; functionally, these signaling pathways belong to the following three categories: 1) steroid and terpenoid biosynthesis, 2) immune response, and 3) cell adhesion/motility. In addition, the expression of several proteins involved in lipid transport was significantly altered in Npc1-/- mice.
2010-08-30 | E-GEOD-20450 | biostudies-arrayexpress
Project description:Macrophage inflammatory protein 1alpha/CCL3 protein is a known pro-inflammatory cytokine that can mediate chemotaxis of monocytes and promote cell degranulation. Ccl3 gene expression is elevated in the CNS and visceral tissue of many lysosomal storage disorders. The deletion of Ccl3 in a mouse model of Sandhoff disease was reported to result in reduced monocyte-associated pathology in the brain, delayed neurodegeneration, and prolonged health. However, deletion of Ccl3 in a mouse model of Niemann-Pick C disease was dentrimental or neutral instead of beneficial. Prevention of neuronal loss was instead mediated by providing NPC1 to neurons. We used microarrays to detail the global change in gene expression of the cerebellum in Niemann-Pick C disease animals, Niemann-Pick C disease animals with Ccl3 gene deletion, and Niemann-Pick C disease animals with Purkinje neuron-specific NPC1-YFP rescue. To identify the top ~50 genes elevated in NPC disease Npc1-/- (NPC) and Npc1+/- (WT) mice were compared at age P50; To profile changes in gene expression as a result of Ccl3 gene deletion Ccl3-/-;Npc1-/- mice were compared against Npc1-/- mice across various ages; To profile changes in gene expression as a result of Purkinje neuron-sepcific NPC1 rescue P;N;Npc1-/- mice were compared against Npc1-/- mice across various ages.
2012-04-16 | E-GEOD-36119 | biostudies-arrayexpress
Project description: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
2007-07-01 | GSE5944 | GEO
Project description: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.
2008-06-14 | E-GEOD-5944 | biostudies-arrayexpress
Project description:1) AJS-ESI source comparison of 2, 10 and 20ug of HeLa digest
2) Label-free analysis of 11-week NPC1 null mice and control for unfractionated cerebellum and cerebral cortex
3) Label-free analysis of 11-week NPC1 null mice and control for fractionated cerebellum
2018-02-25 | MSV000082102 | MassIVE
Project description:Niemann-Pick type C (NPC) disease is an inherited lysosomal storage disorder mainly driven by mutations in NPC1 gene, causing lipid accumulation within late endosomes/lysosomes, and resulting in progressive neurodegeneration. Although microglial activation proceeds neuronal loss, it remains elusive whether loss of NPC1 in microglia actively contributes to NPC pathology. Here, we used a mouse model with depletion of NPC1 in myeloid cells to investigate the role of microglia in Niemann-Pick disease. In order to achieve the loss of NPC1 in myeloid cells, mice with floxed Npc1 alleles (Npc1 flox/flox) were crossed with mice expressing the constitutively active Cre recombinase under the myeloid-specific promotor of Cx3cr1. Hyperactive microglia initiated a pathological cascade resembling NPC-like phenotypes, including shortened lifespan, motor impairments, astrogliosis, neuroaxonal pathology and increased levels of neuronal injury biomarker NF-L. To study the differential vulnerability between the brain regions, we compared the cerebellar with the cerebral (brain without cerebellum) proteome in Cre- and Cre+ mice at late pathological stages. Our results suggest that microglial loss of NPC1 has profound effects on brain cell homeostasis especially in the cerebrum.
2024-12-05 | PXD056188 | Pride
Project description:Label-free quantification of cerebellum and cerebral cortex proteomics in 11 week wild type and NPC1 null mice
2018-02-08 | MSV000082040 | MassIVE
Project description:Differential gene expression in BALB/c Npc1-/- and Npc1+/+ cerebellum
| PRJNA97395 | ENA
Project description:label-free quantification using 11 week mouse tissue lysates from cerebellum and cerebral cortex of wild type and NPC1 null mice.
2018-02-08 | MSV000082039 | MassIVE