Figure 3.

 Phenotypic comparison of K-ras^−/− embryos and control littermates. (A) The wild-type littermate is on the left and the K-ras^−/− littermate is on the right. Note the slight developmental delay (∼0.5 gestational days) and pale coloring of the liver in the K-ras^−/− embryo. (B) The control E18.5 K-ras^+/− embryo is on the left and the K-ras^−/− embryo is on the right. Note the marked reduction in size of the mutant relative to the control littermate as well as the noncoordinate development of the K-ras^−/− embryo. The eyes have not developed beyond E15.5, whereas the limbs, tail, and skin have all advanced to at least E17.5. (C,D) Parasagittal section through an E12.5 K-ras^−/− (C) and a control wild-type (D) fetal liver. Note the areas of hypocellularity in the K-ras mutant fetal liver, whereas the cells are densely packed in the control liver. Also, pyknotic nuclei (white arrows) in the distal portion of the K-ras^−/− hepatic lobe are indicated. (E,F) Cell death analysis on an adjacent fetal liver section from C and D. Note the presence of significant numbers of TUNEL-positive (brown staining) cells in the K-ras^−/− fetal livers (E). In more severely affected embryos, these apoptotic cells were present throughout the liver. In contrast, very few cells stain positive in the TUNEL assay from control fetal livers (F).