Loss of Cbs causes growth defects and hepatic dysfunction in mice. (A) Representative images of WT and Cbs^−/− mice at 14 days of age. (B) Body weight growth curves of Cbs^−/− (n = 9) and WT (n = 10) mice. (C) Kaplan–Meier survival curve of Cbs^−/− mice (n = 30) and WT littermates (n = 30). Median lifespan of Cbs^−/− mice (16.7 ± 0.48 days) is indicated. All WT mice survived beyond the observation period. (D) Homocysteine levels in the liver, plasma, urine, kidney, and brain of WT and Cbs^−/− mice with or without VB12 treatment. n = 3 mice per group. (E) Representative images of the liver in WT and Cbs^−/− mice (left) and quantification of the liver weight as a percentage of body weight (LW/BW ✕ 100) of WT (n = 5) and Cbs^−/− (n = 8) mice. Bars, 2 mm. (F) Oil Red O staining of liver sections from WT and Cbs^−/− mice. Left: Representative images. Right: Quantification of staining intensity. n = 3 mice per group. Bars, 50 μm. (G) H&E staining of liver sections from WT and Cbs^−/− mice. Left: Representative images. Right: Quantification of vacuolated areas. n = 3 mice (WT); n = 4 mice (Cbs^−/−). Bars, 50 μm. (H) Activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in WT and Cbs^−/− mice. n = 3 mice per group. (I) Western blot analysis of CYP1A2 levels in liver lysates from WT and Cbs^-/-mice. GAPDH serves as a loading control. Data are presented as mean ± SEM. Statistical significance was calculated using the two-sided Student’s t test. *P < 0.05, **P < 0.01, and **** P < 0.0001. Source data are available for this figure: SourceData F7.