This transgenic mouse line overexpresses wild type human alpha-synuclein under the regulatory control of the human platelet-derived growth factor–β (PDGF-β) promoter (D-line; Masliah et al. 2000, Science 287: 1265-9). Mice are bred on a C57BL/6 background. These mice replicate features of human synucleinopathies such as abnormal accumulation of alpha-synuclein, increased phosphorylation of alpha-synuclein and high levels of ubiquitin in cortical and subcortical regions of the brain. The distinct histopathological features of these animals allow testing the efficacy of pharmaceutical compounds to interfere with, or even reverse the progression of alpha-synuclein accumulation. Additional immunoreactivity occurs in presynaptic cortical terminals, consistent with its role as a presynaptic protein.
D-Line mice are cryo-preserved and will be recovered upon request.
Figure: Quantitative immunofluorescence (A) reveals increases in human α-synuclein expression over age in D-Line mice in both neocortex and hippocampus. n = 10-12; Mean + SEM. Two-way ANOVA with Bonferroni’s post hoc test. *p<0.05; **p<0.01; ***p<0.001. B: Immunolabeling of phosphorylated human α-syn (red) in the hippocampal CA3 (A) and somatosensory cortex (B) of 7 month old D-Line mice. Phosphorylated human α-syn (red) is targeted to somata of principal neurons in the hippocampal stratum pyramidale (sp) where it accumulates in the nucleus (arrowheads), but is undetectable in neurites. Expression levels in the neocortex are shown in deep layers V and VI close to the white matter (wm). The green channel shows expression of transgenic human α-syn.