Figure 2.

Histopathology of mouse brains defective for the Atp1a2gene.A–C, Sagittal sections of E18.5–P0 fetal brains of wild-type (+/+), heterozygous (+/-), and homozygous (-/-) mutant mice. Representative photographs are shown from multiple brains analyzed of wild-type (n=7), heterozygous (n=7), and homozygous (n=13) mice. Note the decreased cellular density in the homozygous mice (C) that is limited to the amygdala (asterisks), with the exception of the nucleus of the lateral olfactory tract (LOT). Scale bar, 1 mm. D–F, Higher magnification of the amygdala regions shown in A–C, respectively. In the homozygous mutant, the decreased cellular density in the amygdala was bordered by regions of normal cellular density (F, arrowheads). Scale bar, 250 μm. G–I, Increased apoptosis in the brain of homozygous mutant mice. Frontal sections of the brain at E18.5–P0 were stained by TUNEL. The numbers of TUNEL-positive cells in the amygdala and piriform cortex (arrows) were higher in the homozygous brain than in the heterozygous or wild-type brains. In the same sections counterstained with Hoechst 33258, the TUNEL-positive cells had pyknotic nuclei (data not shown). Scale bar, 1 mm. J–L, Electron micrographs of cells in the amygdala (E18.5–P0).Condensed chromatin (K, arrows) typical of apoptotic cells was observed in the homozygous mutant (K,L) but not in the wild-type (J) or heterozygous mutant (data not shown). Two littermates of the wild-type and three of the homozygous were examined. Scale bars: J, K,5 μm; L,2 μm.