Increased expression and aggregated α-synuclein in Smad3-/- mice. (A) Immunoblots of ST and VM tissue show that Smad3 deficiency increases the striatal α-synuclein content (*P < 0.05, Student's t-test with n = 6 mice per genotype, measured in triplicate). (B) Further evaluation of α-synuclein expression by immunohistochemistry along the rostro-caudal axis of the ST. Twenty brain sections per mice were counted from Smad3+/+ (n = 5) and Smad3-/- (n = 6). Figure indicates values for the rostral 1000 μm. O.D. quantification shows an increase in the ST of Smad3 null mice (*P < 0.05, Student's t-test). (C-F) Several nervous system regions from Smad3 wild-type and null mice were subjected to graded detergent extraction (Triton-soluble, SDS-soluble, and SDS-insoluble fractions) and analyzed in Western blots. The molecular weight markers on the left indicate the protein size in kilodaltons (**P < 0.01, Student t-test, n = 3 for Smad3+/+, n = 5 for Smad3-/-, n = 2 for α-synuclein-/- mice).