Figure 3.

Histological and pathological analysis of SC35-deficient hearts. (A) Cell proliferation assay by BrdU labeling. Mice were injected with BrdU at E18.5 and ventricles were isolated 22 h later. Paraffin sections of ventricles were blotted with biotinylated anti-BrdU antibody followed by staining with HRP-conjugated streptavidin in the presence of the substrate AEC. Proliferating cells were stained as brown dots in the periphery of the heart. (B) Isolated mutant hearts and their littermate controls at 3 and 5 weeks after birth (a and b); H&E-stained coronal sections showing normal cardiac histology 3 weeks after birth, but chamber enlargement and cardiomyocyte hypertrophy at postnatal 5 weeks (c–h). (C) Extensive fibrosis and myofibril disarray in SC35-deficient hearts were evident at an advanced stage (a and b). However, the sarcomere structure appeared normal under the electron microscope (c and d). Dramatic heart enlargement and chamber dilation were seen with the SC35 knockout hearts at late stages (c and d). The stages (in months) indicate the time when the hearts were collected for analysis, which do not represent the phenotype onset points.