RGD Reference Report - Early Expression of Parkinson's Disease-Related Mitochondrial Abnormalities in PINK1 Knockout Rats. - Rat Genome Database

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Early Expression of Parkinson's Disease-Related Mitochondrial Abnormalities in PINK1 Knockout Rats.

Authors: Villeneuve, LM  Purnell, PR  Boska, MD  Fox, HS 
Citation: Villeneuve LM, etal., Mol Neurobiol. 2016 Jan;53(1):171-86. doi: 10.1007/s12035-014-8927-y. Epub 2014 Nov 25.
RGD ID: 11560775
Pubmed: PMID:25421206   (View Abstract at PubMed)
PMCID: PMC4442772   (View Article at PubMed Central)
DOI: DOI:10.1007/s12035-014-8927-y   (Journal Full-text)

PTEN-induced kinase 1 (PINK1) mutations are responsible for an autosomal recessive, familial form of Parkinson's disease. PINK1 protein is a Ser/Thr kinase localized to the mitochondrial membrane and is involved in many processes including mitochondrial trafficking, mitophagy, and proteasomal function. Using a new PINK1 knockout (PINK1 KO) rat model, we found altered brain metabolomic markers using magnetic resonance spectroscopy, identified changes in mitochondrial pathways with quantitative proteomics using sequential window acquisition of all theoretical spectra (SWATH) mass spectrometry, and demonstrated mitochondrial functional alterations through measurement of oxygen consumption and acidification rates. The observed alterations included reduced creatine, decreased levels of complex I of the electron transport chain, and increased proton leak in the electron transport chain in PINK1 KO rat brains. In conjunction, these results demonstrate metabolomic and mitochondrial alterations occur during the asymptomatic phase of Parkinson's disease in this model. These results indicate both potential early diagnostic markers and therapeutic pathways that can be used in PD.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
LE-Pink1em1Sage-/-RatParkinson's disease  IMP  RGD 
PINK1HumanParkinson's disease  ISORGD:1305769 RGD 
Pink1RatParkinson's disease  IMP  RGD 
Pink1MouseParkinson's disease  ISORGD:1305769 RGD 
Pink1em1SageRatParkinson's disease  IMP  RGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Pink1Ratmitochondrial fission  HMP  RGD 
Pink1Ratnegative regulation of fatty acid beta-oxidation  HMP  RGD 

Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
LE-Pink1em1Sage-/-Ratdecreased substantia nigra cell number  IMP compared to LEHRGD 
Pink1Ratdecreased substantia nigra cell number  IMP compared to LEHRGD 
Pink1em1SageRatdecreased substantia nigra cell number  IMP compared to LEHRGD 
LE-Pink1em1Sage-/-Ratdecreased substantia nigra size  IMP compared to LEHRGD 
Pink1Ratdecreased substantia nigra size  IMP compared to LEHRGD 
Pink1em1SageRatdecreased substantia nigra size  IMP compared to LEHRGD 
LE-Pink1em1Sage-/-Ratincreased oxygen consumption onsetIMP compared to LEHRGD 
Pink1Ratincreased oxygen consumption onsetIMP compared to LEHRGD 
Pink1em1SageRatincreased oxygen consumption onsetIMP compared to LEHRGD 
Objects Annotated

Genes (Rattus norvegicus)
Pink1  (PTEN induced kinase 1)
Pink1em1Sage  (PTEN induced putative kinase 1; zinc finger nuclease induced mutant 1, Sigma Advanced Genetic Engineering Labs)

Genes (Mus musculus)
Pink1  (PTEN induced putative kinase 1)

Genes (Homo sapiens)
PINK1  (PTEN induced kinase 1)

Strains
LE-Pink1em1Sage-/-  (NA)


Additional Information