Supplementary Figure 5: Phenotypic characterization of mice after Lmx1a, Lmx1b and Lmx1a/b ablation in mature mDA neurons.
From: Dopaminergic control of autophagic-lysosomal function implicates Lmx1b in Parkinson's disease
(a) TH immunostaining in striatal sections of 2 months (2m) old cLmx1a/bDatCreERT2, cLmx1aDatCreERT2, cLmx1bDatCreERT2 mice and their corresponding control littermates (cLmx1a/bCtrl, cLmx1aCtrl and cLmx1bCtrl). All mice were treated with tamoxifen (TAM) at 4 weeks of age and analyzed 4 weeks later. cLmx1a/bDatCreERT2 and cLmx1bDatCreERT2 show abnormally large TH-immunopositive profiles throughout the striatum (arrows). Scale bar, 50 μm. n= 2 cCtrl and 4 cLmx1aDatCreERT2; n= 4 cCtrl and 7 cLmx1bDatCreERT2; n= 6 cCtrl and 6 cLmx1a/bDatCreERT2. (b-c) Quantification of the number of synaptic vesicles (sv) per µm of active zone (az) and of the number of multilamellar autophagic-lysosomal vesicles (ALV) per µm2 of the terminal profile in TH-immunostained striatal terminals larger than 1 µm from serial ultrathin sections of cLmx1a/bCtrl (cCtrl) and cLmx1a/bDatCreERT2 (cERT2) mice. n=5 synapses per genotype; n= 2 animals per genotype. (d-g) Battery of behavioral tests performed with cCtrl and cERT2 mice 6 months after TAM treatment. Beam traversal test (d) and Pole test (e) indicate no significant impairments of motor coordination and postural control. Open field test (f) shows no major alteration in locomotor activity. Novel object recognition test (g) shows no impairment in short-term memory formation since both groups show a significant preference for the novel object. Mice were aged 6 to 9 months. n=14 cCtrl and 16 cERT2 animals; All data is represented as mean±sem; Mann Whitney test was applied in (b-c), Unpaired t test was applied in (d-f), one sample t test was applied in (g); *p<0.05, **p<0.005, ***p<0.0005.
