Fig. 4.

Correlation of hASM expression and reversal of pathology in the brain. Shown are sagittal tissue sections of the striatum from the AAV2 brain-alone (A, C, and E), combination (B, D, and F), and untreated ASMKO (G) and wild-type (H) groups. Brain sections were processed by in situ hybridization to determine the site of transduction (A and B), by immunohistochemistry to detect hASM (C and D), and by lysenin to detect SPM (E–H). The hASM human mRNA and protein patterns in the AAV2 brain-alone group roughly overlapped with the area of SPM clearance (arrow). In contrast, animals from the combination group showed clearance of SPM (arrow) that extended beyond the transduction site. On closer examination, a faint and diffuse hASM pattern that may correspond to cross-correction was observed in the combination group (asterisk). This diffuse hASM pattern was not observed in the AAV2 brain-alone group (asterisk), indicating that cross-correction may have been compromised in this group. All photographs were exposure-matched for accurate comparisons. (Scale bar: 0.25 mm.)