Table 2.
Comparative overview of existing murine transgenic models of MSA summarizing salient behavioural and neuropathological features.
| Transgenic mouse model of MSA | Genetic design | Behaviour | Pathology | References |
|---|---|---|---|---|
| (PLP)-αSYN | Human αSYN overexpression under the PLP promoter | Shortened stride length Exacerbated phenotype with impaired rearing, pole test, hindlimb and truncal dystonia, bradikinesia |
GCIs Degeneration of SNc, LC, NAmb, LDT, PPT, and Onuf's nucleus Microglial activation 3NP exacerbated phenotype with SND and OPCA, astrogliosis |
(Kahle et al., 2002; Stefanova et al., 2005a, Stefanova et al., 2007) |
| (MBP)-αSYN | Human αSYN overexpression under the MBP promotor | Tremor Ataxia Impaired rotarod and pole test Seizures |
GCIs Astrogliosis Demyelination Axonal and dendritic degeneration in the cortex Reduced TH fiber density in striatum without loss of SNc dopaminergic neurons |
(Shults et al., 2005) |
| (CNP)-αSYN | Human αSYN overexpression under the CNP promotor | Impaired rotarod performance Impaired wire hanging |
GCIs Demyelination and secondary axonal degeneration Neuronal loss in hippocampus and cortical areas |
(Yazawa et al., 2005) |
| α1B-AR | α1B-AR overexpression under the mouse α1B-AR promoter | Decreased horizontal ambulation Decreased rearing (partly reversible by L-DOPA) Tremor Seizures Decreased heart rate Hypotension Increased in vivo spontaneous interictal epileptogenicity and EEG/behavioural seizures |
Granulovacular degeneration in all areas of the brain Neuronal and oligodendroglial αSYN aggregation Cardiac hypertrophy Reduced catecholamine plasma levels |
(Zuscik et al., 2000, 2001; Papay et al., 2002; Kunieda et al., 2002) |
αSYN, α-synuclein; α1B-AR, α1B adrenergic receptor; PLP, proteolipid protein; MBP, myelin basic protein; CNP, 2',3'-cyclic nucleotide 3'-phosphodiesterase; EEG, GCIs, glial cytoplasmic inclusions; SNc, substantia nigra pars compacta; LC, locus coeruleus; NAmb, nucleus ambiguus; LDT, laterodorsal tegmental nucleus; PPT, pedunculopontine tegmental nucleus; SND, striatonigral degeneration; OPCA, oligopontocerebellar atrophy; TH, tyrosine hydroxilase.