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Proteomics of brain from a myeloid specific NPC1 KO mouse

ABSTRACT: 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.

INSTRUMENT(S): timsTOF Pro

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Brain

DISEASE(S): Niemann-pick Disease Type C1,Niemann-pick Disease

SUBMITTER: Stephan Mueller

LAB HEAD: Dr. Stefan F. Lichtenthaler

PROVIDER: PXD056188 | Pride | 2024-12-05

REPOSITORIES: Pride

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			Action	DRS
	DIA-NN_cerebellum.zip	Other
	DIA-NN_cerebrum_stem.zip	Other
	F_Cb_01_Slot1-32_1_5118.d.zip	Other
	F_Cb_02_Slot1-33_1_5120.d.zip	Other
	F_Cb_03_Slot1-34_1_5123.d.zip	Other

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