RGD Reference Report - iPLA2ß knockout mouse, a genetic model for progressive human motor disorders, develops age-related neuropathology. - Rat Genome Database

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iPLA2ß knockout mouse, a genetic model for progressive human motor disorders, develops age-related neuropathology.

Authors: Blanchard, Helene  Taha, Ameer Y  Cheon, Yewon  Kim, Hyung-Wook  Turk, John  Rapoport, Stanley I 
Citation: Blanchard H, etal., Neurochem Res. 2014 Aug;39(8):1522-32. doi: 10.1007/s11064-014-1342-y. Epub 2014 Jun 12.
RGD ID: 12910702
Pubmed: PMID:24919816   (View Abstract at PubMed)
PMCID: PMC4364003   (View Article at PubMed Central)
DOI: DOI:10.1007/s11064-014-1342-y   (Journal Full-text)

Calcium-independent phospholipase A2 group VIa (iPLA2ß) preferentially releases docosahexaenoic acid (DHA) from the sn-2 position of phospholipids. Mutations of its gene, PLA2G6, are found in patients with several progressive motor disorders, including Parkinson disease. At 4 months, PLA2G6 knockout mice (iPLA2ß(-/-)) show minimal neuropathology but altered brain DHA metabolism. By 1 year, they develop motor disturbances, cerebellar neuronal loss, and striatal α-synuclein accumulation. We hypothesized that older iPLA2ß(-/-) mice also would exhibit inflammatory and other neuropathological changes. Real-time polymerase chain reaction and Western blotting were performed on whole brain homogenate from 15 to 20-month old male iPLA2ß(-/-) or wild-type (WT) mice. These older iPLA2ß(-/-) mice compared with WT showed molecular evidence of microglial (CD-11b, iNOS) and astrocytic (glial fibrillary acidic protein) activation, disturbed expression of enzymes involved in arachidonic acid metabolism, loss of neuroprotective brain derived neurotrophic factor, and accumulation of cytokine TNF-α messenger ribonucleic acid, consistent with neuroinflammatory pathology. There was no evidence of synaptic loss, of reduced expression of dopamine active reuptake transporter, or of accumulation of the Parkinson disease markers Parkin or Pink1. iPLA2γ expression was unchanged. iPLA2ß deficient mice show evidence of neuroinflammation and associated neuropathology with motor dysfunction in later life. These pathological biomarkers could be used to assess efficacy of dietary intervention, antioxidants or other therapies on disease progression in this mouse model of progressive human motor diseases associated with a PLA2G6 mutation.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
neurodegenerative disease  ISOPla2g6 (Mus musculus)12910702; 12910702 RGD 
neurodegenerative disease  IMP 12910702 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Pla2g6  (phospholipase A2 group VI)

Genes (Mus musculus)
Pla2g6  (phospholipase A2, group VI)

Genes (Homo sapiens)
PLA2G6  (phospholipase A2 group VI)


Additional Information