General Information

Mouse: 129/SvEv

Mice bearing the pathogenic human G309D-PINK1 mutation inserted by homologous recombination in the orthologous mouse PINK1 locus. Insertion of the probe results in the transcription of unstable mRNA and no PINK1 protein expression is detected in transgenic animals.

Corresponding human genotype: G309D missense mutation have been detected in PD patients. Autosomal recessive mutation in the PINK1 gene leading the early-onset Parkinson’s disease characterized by loss-of-function of the PINK1 protein (PARK6).

Mutated gene: PINK1

References: Gispert 2009

Neurodegeneration

  • 18 months: normal morphology and no loss of TH-positive neurons is observed in the SN. A reduction of TH-positive nerves terminals is detected in the striatum.

Dopamine Homeostasis

  • 9 and 22-24 months: reduction in the levels of dopamine is observed in the striatum.

Inclusions

  • 16 months: No alpha-synuclein aggregates are observed in the brain but an increased expression of alpha-synuclein is detected in the dorsal motor nucleus of the vagus (somatodendritic localisation).
  • 24 months: increased expression of alpha-synuclein protein in the brainstem and midbrain with however a reduced mRNA expression in the same regions. This data indicate that clearance of the protein is affected in the mutant mice.

Motor Behaviours

  • 0-15 months: no evident alteration of locomotor activity is observed. (Note that this may be related to the fact that the wild type 129/SvEv mice are known for their low motor activity)
  • 16 months: impairment of spontaneous movement measure in the open field test. A reduction in total distance, horizontal activity, movement time are decreased by about 30%.

Response to dopaminergic treatment

  • Not reported

Non motor Behaviours

  • 12 months: significant loss of weight reaching 19% reduction is observed.
  • 16 months: non-motor dysfunctions were not observed in different tests (sweating, startle reflexes to acoustic stimuli
  • Mitochondrial dysfunctions are detected in vitro using tissue-isolated mitochondria from the transgenic mice

Electrophysiology

  • Not reported

Neuroinflammation

  • Not reported

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