Figure 3.

Correction of brain after gene therapy

(A) IDS enzyme activity in brain. (B) Mass spectrometry quantification of total brain heparan sulfate. (C) Relationship between brain heparan sulfate content and vector copy number in bone marrow. (D) Non-linear regression between brain heparan sulfate content and IDS enzyme activity in brain. (E) Representative examples of Alcian blue-positive areas in brain areas of untreated Ids^y/− mice and matched WT controls. Scale bar, 50 μm. (F) Quantification of Alcian blue staining in different regions of the brain after gene therapy by counting positive cells. Representative examples of Alcian blue staining after gene therapy are shown in Figure S4. (G) Quantification of Alcian blue-positive staining using a scoring system (see Table S2) in choroid plexus and meninges after gene therapy. Data are presented as means ± SEM. In (A) and (B) data were analyzed by one-way ANOVA with Bonferroni’s correction. In (F) data were analyzed by two-way ANOVA with Bonferroni’s correction, using treatment (IDSco, IDS.IGF2co, IDS.ApoE2co, or IDS.RAP12x2co) and brain areas as categorical variables. Regression analysis of (C and D) is shown in Table S1. Asterisks represent significance vs. WT; hashmarks represent significance vs. Ids^y/−. Other significant comparisons are identified by brackets. PV, perivascular cells; PC, parenchymal cell; Mg, meninges; CP, choroid plexus; PN, perineuronal net. (A–D) Experiment 1: n = 5 or 6 per group. Experiment 2: IDSco, IDS.IGF2co, GFP, Ids^y/− and WT n = 6; IDS.ApoE2co n = 10; IDS.RAP12x2co n = 7. (F and G) n = 3. ∗p ≤ 0.05, ∗∗p ≤ 0.01, ∗∗∗p ≤ 0.001, ∗∗∗∗p ≤ 0.0001. #p ≤ 0.05, ###p ≤ 0.001, ####p ≤ 0.0001.