General Information

Mouse: CB57BL/6 x B6C3H

Conditional expression of the  human wild type alpha-synuclein protein under the control of the Calcium/calmodulin-dependent protein kinase IIa promoter (CaM) and the tetracycline-regulated tet-off system (tTA).

Endogenous alpha synuclein: Yes

Corresponding human genotype: Autosomal dominant mutation in PD patients (PARK1/PARK4)

Transgene insertion:  not specified

References: Nuber 2008, Lim 2010

Transgene expression

  • Expression of human alpha-synuclein is observed in forebrain and midbrain with 1-3 x increase compared to littermate wild type mice.
  • Expression of human alpha-synuclein can be blocked by giving mice doxycycline in drinking water (Nuber 2008) or chow (Lim 2010)

Neurodegeneration

  • P21: Atrophy in post mitotic DG hippocampal neurons is observed.
  • 9 months: Very moderate, but not statistically significant, loss of TH-positive neurons (around 15%) is detected compared to control mice

Dopamine Homeostasis

  • 25 months: a decrease in DA levels is observed in the olfactory bulb; some reduction is also detected in the SN but does not reach statistical significance.

Inclusions

  • No inclusions are observed at any time points in this model
  • 12 and 18 months: high cytoplasmic expression of hsynwt protein in the SN is observed

Motor Behaviours

  • 30 weeks: start of progressive motor decline is observed. This deficit can be reduced,  in aged-animals 8(58 weeks-old) by giving mice doxycycline which prevents human alpha-synuclein over-expression

Response to L-DOPA treatment

  • Not reported

Non motor Behaviours

  • 12 months : some alterations in long term memory and spatial learning, assessed by the Morris Water Maze, are observed compared to wild type littermates

Electrophysiology

  • Not reported

Neuroinflammation

  • Not reported

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