Saccharopine accumulation leads to mouse liver hypertrophy and defective postnatal growth. (A) Representative images of WT, Aass(R65Q), and Aass(G489E) mice at P40. (B) Growth curves of WT, Aass(R65Q), and Aass(G489E) knock-in mice. n = 7. (C) Survival curves of postnatal WT, Aass(R65Q), and Aass(G489E) mice. n = 7. (D and E) Plasma lysine (D) and saccharopine (E) levels in WT, Aass(R65Q), and Aass(G489E) mice. Data (mean ± SEM) are from four mice (as measured in Fig. S4 C) and are normalized to the WT value. (F) Quantitative real-time PCR analysis of Aass expression in different mouse tissues. Data (mean ± SEM) are from four independent experiments and are normalized to the Gapdh value. (G) Western blot of AASS protein in the livers of WT, Aass(R65Q), and Aass(G489E) mice. α-Tubulin was used as the internal control. Three animals were analyzed for each genotype. (H and I) Plasma ALT (H) and AST (I) activities of WT, Aass(R65Q), and Aass(G489E) mice. Data (mean ± SEM) are from four or more mice at P40. (J) Images (left) and ratio of liver to body weight of WT and Aass(R65Q) (top) and of WT and Aass(G489E) (bottom) mice at P40. n = 4. (K and L) Lysine (K) and saccharopine (L) levels in the livers of WT, Aass(R65Q), and Aass(G489E) mice. Data (mean ± SEM) are from four mice (as measured in Fig. S4 D). Error bars represent SEM.