Proteome of the cortex of old Pink1-SNCA A53T double mutant Parkinson mice
Ontology highlight
ABSTRACT:
INSTRUMENT(S):
ORGANISM(S): Mus Musculus (mouse)
TISSUE(S): Brain
DISEASE(S): Parkinson's Disease
SUBMITTER: 
Ilka Wittig
LAB HEAD: Irmgard Tegeder
PROVIDER: PXD039172 | Pride | 2025-10-21
REPOSITORIES: Pride
Dataset's files
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| P18_008_Parkin_B_KO1.raw | Raw | |||
| P18_008_Parkin_B_KO2.raw | Raw | |||
| P18_008_Parkin_B_KO3.raw | Raw | |||
| P18_008_Parkin_B_KO4.raw | Raw | |||
| P18_008_Parkin_B_KO5.raw | Raw |
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Project description:Parkinsons's Diseases causes early pre-motor somatosensory manifestations of the disease, leading to a sensory polyneuropathy with sensory loss and chronic pain. We assessed gene gene regulation in the dorsal root ganglia (DRGs) of aged-old Pink1SNCA double mutant mice by comparing RNA-seq expression profiles. Pink1SNCA mice are a model for Parkinsons's Disease (PD) carrying a Pink1 deletion plus transgene overexpression of human mutant alpha-synuclein. Homozygous Pink1-/-,SNCA A53T double mutant mice were generated by crossing Pink1-/- mice (background: 129/SvEv) with A53T-SNCA-overexpressing mice (background: FVB/N) and then, interbreeding the littermates. They contain 129/SvEv and FVB/N genetic backgrounds approximately in a 50:50 distribution. Wildtype control mice (FVBSv) are hybrids from a crossbreeding of 129/SvEv and FVB/N mice, which were descended from littermates of double mutant mice. RNAseq was performed in two sequential experiments with 4/4 old and 4/5 aged wildytpe and Pink1SNCA mice, respectively. The alignment was done consecutively. For analysis both sets were combined. A total number of 25702 genes was reliably detected in both datasets, and 22784 passed the filtering criteria of >7 valid samples in total. GSEA gene set enrichment analysis was used for gene ranking and identication of top up- and downregulated genes and evaluation of their functions based on P-value, Q-value, fold change and abundance. Apart from the knockout of Pink1, a prominent down-regulated gene was acidic fibroblast growth factor, Fgf1, which is known to restore the survival of dopaminergic neurons in PD models. Up-regulated genes included DNase1l3, CCL27 and CCL25, IFI44 and IL31ra, and pointed to increased DNAse activity and activation of the immune system.
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