Figure 4.

Accumulation of amorphous and membranous material in neuronal perikarya, dendrites, and axons in cathepsin B^−/−/L^−/− mice. (a and b) LFB stain of P11.5 and P15.5 double-mutant cortical neurons. At P11.5 (a), only a few inclusions are observed in some neuronal perikarya (arrow). The arrowhead points to a normal neuron. Only a few days later, at P15.5 (b), the perikarya are expanded and filled with LFB-positive inclusions. (c–e) Electron micrographs of inclusions in P12.5 (c and d) and P24.5 (e) cathepsin B^−/−/L^−/− cortical neurons. (d) Higher magnification of the inclusion indicated by an arrow in c. (f) Sagittal section of the P11.5 double-knockout brain shown in a revealing a dense accumulation of eosinophilic globules in cerebral white matter (H&E stain). (g and h) Magnification of the area surrounding the asterisk shown in f stained with H&E and LFB, respectively. Normal white matter is seen in the upper right corner. All LFB stainings were performed simultaneously. (i) Electron micrograph of membranous inclusions in a swollen axon in the corpus callosum of a P12.5 cathepsin B^−/−/L^−/− mouse. [Scale bars = 15 μm (a, b, g, h), 2 μm (c), 100 nm (d), 1.6 μm (e), 0.15 mm (f), and 500 nm (i).]