These mice develop age-dependent severe motor impairments leading to death and widespread α-synuclein neuronal inclusions [ 11, 15].
Although some α-synuclein transgenic mice develop similar clinical signs of the spinal cord pathology to γ-synuclein transgenic mice, neither down-regulation of HSPB1 nor changes of the neurofilament network in their motor neurons has been reported.
Human α-synuclein transgenic mice lacking mouse α-synuclein expression was generated by successive mating of human α-synuclein transgenic mice, congenic for C57BL6 strain (N10), to mice lacking endogenous α-synuclein [41] that were procured from Jackson labs.
The percentage of mice that developed phosphorylated α-synuclein pathology in the injected side of the brains was 50% in the group injected with insoluble phosphorylated α-synuclein of dementia with Lewy bodies brains, which is less than that in mice injected with recombinant α-synuclein fibrils (Table 2).
Strikingly, all the mice injected with mouse α-synuclein fibrils developed phosphorylated α-synuclein pathology in the injected side of the brain, whereas no pathology was detected in mice injected with soluble mouse α-synuclein (Table 2).
Hemizygous TgM83+/− mice that do not carry the Gfap-luc transgene develop pathological α-synuclein deposition in the CNS at 22 28 months of age.
Consistent with a previous report, a few homozygous mice expressing A53T α-synuclein developed a progressively severe motor phenotype at 8 months of age.
C57BL/6J mice injected with α-synuclein fibrils developed abundant Lewy body/Lewy neurite-like pathology, whereas mice injected with soluble α-synuclein did not.
Transgenic mice from line G2-3(A53theexpress transgenegene at approximately six times the level of endogenous mouse α-synuclein and develop a fatal neurodegenerative disease with an average life span of ∼12 months [11].
Interestingly, mice lacking α-synuclein are resistant to mitochondrial toxins [31], [42] whereas human A53T α-synuclein-overexpressing mice are known to develop neuronal mitochondrial degeneration and cell death through induction of oxidative stress [43], [44].
