Figure 3.

GYS2-1 Treatment Results in a Normalization of Liver Pathology in an Agl^−/− GSD III Mouse Model

(A) Agl^−/− mice treated with PBS or GYS2-1 weekly for 18 doses starting at 8 weeks of age. Histological analysis was performed using H&E and PAS staining as indicated. Ki67-positive cells and infiltrated mononuclear cells (H&E:M) were noted in Agl^−/− mice. Immunohistochemistry for α-smooth muscle actin (α-SMA) and Sirius Red staining were performed to detect stellate cell activation and fibrosis. Representative images of four individual animals from PBS- or GYS2-1-treated groups are shown. The scale bars represent 100 μm. (B) Double staining of Ki67 (dark brown) and CYP3A (cytochrome P450 3A, magenta) or α-SMA (magenta) was performed to detect cell proliferation in both hepatocytes and non-hepatocytes in livers of Agl^−/− mice. (C) Quantitative analysis of immunohistochemistry of Ki67, α-SMA, and Sirius Red (*p ≤ 0.05) staining shown in (A) is shown. Detailed methodology of quantitative analysis can be found in Supplemental Information and Figures S4–S6. Data are presented as mean ± SD. Unpaired t test for statistical significance relative to PBS treatment group or wild-type animals (*p ≤ 0.05) is shown.