Fig. 6: Ufd1s-deficiency leads to liver defects and exacerbates NASH progression.

a Strategy of CRISPR/Cas9-mediated Ufd1s-deficient (Ufd1s^−/−) mice. Genotyping primers and the representative PCR image are shown (three independent experiments), PCR products were further confirmed by Sanger sequencing. b Ipmk protein levels in WT and Ufd1s^−/− mouse livers (N = 3 mice). c Ipmk protein levels of WT mouse livers under normal or 24 h-starved conditions (N = 3 mice). d Representative H&E staining, LC3 immunohistochemistry (IHC) and Oil Red O staining images of liver sections from WT or Ufd1s^−/− mice (N = 3 mice) under normal or 24 h-starved conditions. Nuclear (Nuc)/cytoplasmic (Cyto) area ratio (%) was measured based on H&E staining. AOD average optical density, scale bar, 50 μm. e Schematic illustration of inducing NASH mice model with the methionine and choline-deficient diet (MCD). Serum triglycerides, total cholesterol (f), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) (g) levels of WT and Ufd1s^−/− mice (N = 6 mice), under normal or NASH conditions. h Representative images and quantification of H&E, Oil Red O, Masson staining, Ipmk, and LC3 IHC of liver sections of WT or Ufd1s^−/− mice (N = 6 mice), under normal or NASH conditions. Scale bar, 50 μm. i Representative UFD1s IHC images and quantification in liver sections from clinic non-NASH and NASH specimens (N = 8 clinic specimens). Images from 1 of the 8 non-NASH and NASH specimens are shown, and images from the other specimens are demonstrated in Supplementary Fig. 8i. Scale bar, 50 μm. The number of mice or clinic specimens is denoted by N; data are shown as mean ± SEM. P values were calculated by two-tailed Student′s t-test. Source data are provided as a Source Data file.