Pitx3-AAV2 – Mouse

General Information

Mouse: CB57BL/6

Mice in which the Pitx3 adeno-associated-virus serotype 2 (Pitx3-AAV2) was used to selectively overexpress the Pitx3 protein in midbrain neurons. Adult mice (12 weeks) were transduced bilaterally.

Corresponding human genotype: no association has been found betweenPitx3 overexpressing variants and PD. It cannot be excluded that overexpression of Pitx3 may combine with environmental factors to enhance susceptibility to toxic insults.

Protein overexpressed: Pitx3

References: Kim 2014

Loss of dopaminergic neurons

  • 3 weeks post transduction: a robust expression of Pitx3 protein is observed in the SN and VTA. significant reduction of tyrosine hydroxylase and dopamine transporter expression in both the SNc and the VTA.
  • At 2, 4 and 6 months post transduction: no neurodegeneration and no changes in the number of TH-positive cells are observed in the SN and VTA at any time point.
  • 2 months post transduction: significant upregulation of genes involved in midbrain neuronal functions, including TH, DAT, as well as alpha-synuclein overexpression, is observed. Interestingly, Nurr1 and En1 gene overexpression is also observed

Dopamine Homeostasis

  • 3 months post transduction: Increase of dopamine and dopamine metabolite levels are observed in the striatum and nucleus accumbens. Dopamine release in response to amphetamine is increased.

Inclusions

  • Not reported

Motor Behaviours

  • 3 months post transduction: mice exhibit increased spontaneous locomotor activity in the open field test. No differences are observed on day1 in the rotarod test but Pitx3-AAV2 mice show no improvement of their performance over time suggesting impaired motor learning.

Response to dopaminergic treatment

  • not reported

Non motor Behaviours

  • 3 months post transduction: mice exhibit increased anxiety-like behavior in the open field test as evidenced by an increase in the time spent at the center of the field. in the open field test.

Electrophysiology

  • not reported

Neuroinflammation

  • Not reported
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