Figure 2.

CNS Transduction in MPS-IIIA Mice Injected with AAV9 Bearing IDSspSGSH-IRES-SUMF1 Transgene

(A) P60 MPS-IIIA mice were i.c.v. injected with 4.5 × 10¹² GCs/kg of AAV9 encoding either IDSspSGSH and SUMF1 or GFP. Five different slices covering the main CNS regions (A–E; as described in Figure S1) were collected at both 1 (ETP) and 7 months (LTP) after injection. Sulfamidase activity was measured in these areas and expressed as percentage of the activity found in age-matched WT injected with AAV9 encoding GFP. n = 6–7 animals for each group. Data represent mean ± SEM. *p < 0.05, **p < 0.01, ***p < 0.00 versus MPS-IIIA GFP-treated. One-way ANOVA followed by Tukey’s post hoc test. (B) Anti-human sulfamidase immunostaining in representative brain regions of MPS-IIIA mice was shown at both ETP and LTP upon i.c.v. injection. Scale bar: 100 μm. (C) Co-immunofluorescence analysis of human sulfamidase together with either GFAP (astroglial marker) or NeuN (neuronal marker) in the hippocampus of MPS-IIIA mice injected with AAV9 encoding GFP or IDSspSGSH-IRES-SUMF1 expression cassette. Scale bar: 50 μm.