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