| 57320 |
Q99LX0 |
PARK7_MOUSE |
Parkinson disease protein 7 homolog (Maillard deglycase) (Parkinsonism-associated deglycase) (Protein DJ-1) (DJ-1) (Protein/nucleic acid deglycase DJ-1) (EC 3.1.2.-, EC 3.5.1.-, EC 3.5.1.124) |
DISRUPTION PHENOTYPE |
Increased sensitivity of embryonic cortical neurons to oxidative stress. Age-dependent increase in mitochondrial hydrogen peroxide production and reduced mitochondrial aconitase activity. Down-regulation of Slc25a14 and Slc25a27, compromised calcium-induced uncoupling and increased oxidation of mitochondrial matrix proteins specifically in the dopaminergic neurons of the substantia nigra pars compacta. Reduced N2el2 protein expression. Impaired mitochondrial function and morphology with reduced autophagy leading to accumulation of defective mitochondria. Targeted knockouts in astrocytes exhibit augmented LPS-induced CRK/p38 phosphorylation and signaling, they don't stimulate TLR4 endocytosis upon LPS stimulation. Knockout animals present increased bacterial burdens, reduced local and systemic inflammation, macrophage paralysis and impaired induction of pro-inflammatory cytokines, such as IL6 and TNF, under the condition of sepsis (PubMed:26021615). Mutants from 12 weeks old, but not younger, show higher levels of reactive oxygen species (ROS) and mitochondrial fragmentation in pancreatic islets. They have lower levels of plasma insulin after glucose challenge, display glucose intolerance and have reduced beta-cell area. Younger mutants kept on a high fat diet also show lower levels of plasma insulin, display glucose intolerance and have reduced beta-cell area (PubMed:22611253). Animals become diabetic upon multiple low doses of streptozotocin with reduced insulin concentrations, higher fasting blood glucose concentrations and higher rates of beta cell apoptosis compared to wild type (PubMed:26422139). {ECO:0000269|PubMed:15784737, ECO:0000269|PubMed:17015834, ECO:0000269|PubMed:17766438, ECO:0000269|PubMed:20186336, ECO:0000269|PubMed:21068725, ECO:0000269|PubMed:22611253, ECO:0000269|PubMed:23847046, ECO:0000269|PubMed:26021615, ECO:0000269|PubMed:26422139}. |