Figure 7.

Silencing of Gys2 mRNA Expression Reduces Glycogen Accumulation and Restores Normal Liver Morphology in a L-G6pc^−/− GSD Ia Mouse Model

L-G6pc^−/− mice were dosed intravenously with PBS or GYS2-2 (Gys2 siRNA formulated in lipid nanoparticle) weekly for 5 weeks. Liver samples were collected 48 hr following the final dose. (A) RT-PCR analysis was performed to measure Gys2 mRNA expression in L-G6pc^−/− mice (****p < 0.0001). (B) Measurement of glycogen content in liver extracts was performed in L-G6pc^−/− mice (**p ≤ 0.01). (C) Glucose-6-phosphate levels were measured in L-G6pc^−/− mice treated with PBS or GYS2-2. (D) Quantitative analysis of Ki67-positive liver cells in L-G6pc^−/− mice. Numbers (N) of male (M) and female (F) animals in each group are indicated. (E) Histological analysis to characterize histopathology of L-G6pc^−/− mice using H&E, Oil Red O staining, and Ki67 immunohistochemistry. Liver samples stained with both Oil Red O and hematoxylin (Oil Red O + H) are indicated. Representative images of three individual animals from PBS- or GYS2-2-treated groups are shown. The scale bar represents 100 μm. Data are presented as mean ± SD. Unpaired t test for statistical significance relative to PBS control group.