Figure 7. PEGC15S administration rescues complete CBS-KO mice from early lethality.

(A) Kaplan-Meier survival curve of KO mice that were injected twice weekly with PEGC15S (n = 30) versus mice injected with PBS (n = 16). Mice were maintained on betaine water until day 21. A log-rank test was used for comparison of the 2 survival curves, and significance was calculated using the χ² test. (B) Liver histology results for 2 PEGC15S-injected KO mice that were sacrificed on day 35 versus liver histology results for 2 PBS-injected KO animals that died on days 17 and 24 (H&E staining). Low-magnification views of the liver parenchyma (left panels) show moderate changes, with slightly irregular liver cell plates and mild-to-moderate steatosis, in PEGC15S-injected KO-1 and KO-2 mice, contrasting with massive zonal necroses of hepatocytes (KO-3 mouse, marked by arrowheads) and diffuse steatosis, with multiple dispersed hepatocellular necroses (KO-4 mouse, necroses marked by arrowheads) in the PBS-injected KO mice. A specific stain for apolar lipids in the cytoplasm of hepatocytes is shown in the insets. Higher-magnification views (right panels) demonstrate the presence of frequent mitoses (marked by arrows and shown in detail in the insets) and enlarged pleiomorphic nuclei, with prominent nucleoli in hepatocytes, in the PEGC15S-injected KO mice. Higher-magnification views of the liver parenchyma in PBS-injected KO mice demonstrate confluent hepatocellular necroses, with a sparse inflammatory infiltration (KO-3 mouse, marked by arrowheads) or multiple dispersed necroses, accompanied by a prominent resorptive inflammatory reaction (KO-4 mouse, marked by arrowheads). The remaining liver parenchyma show micro- and macrovesicular steatosis in PBS-injected KO mice. CV, central vein; PT, portal tract. Scale bars: 200 μm (low-magnification images); 100 μm (high-magnification images); and 50 μm (insets).