Pathological analysis of l2hgdh^-/- mice.

The figure compares the histological and ultrastructural appearance of the brain of l2hgdh^+/+ (left panels: A, B, E, G, H, K, L) and l2hgdh^-/- mice (right panels: C, D, F, I, J, M, N). Hematoxylin and eosin staining shows low-magnification of the lateral part of the brain (A, C) at the level of the lateral ventricle (LV), the caudate putamen (striatum; CPu) and the anterior commissure, anterior part (aca). Higher magnification of pencils of Wilson are shown in panels B and D. Notice the satellite oligodendrocyte at B (arrow). Luxol fast blue staining of myelin is shown in E and F, highlighting the predominant presence of vacuoles in the pencils of Wilson of the striatum of the l2hgdh^-/- mouse. Panels G-J are microphotographs from the junction between cortex and white matter in the vicinity of corpus callosum. Immunostaining of NeuN (G and I) shows that most vacuoles in the l2hgdh^-/- mice are at distance from the nucleus of neurons (notice the abundance of vacuoles in the lower part of panel I, devoid of neurons) although a few vacuoles indent the nucleus of some neurons (arrowheads). However, the nucleus of satellite oligodendrocytes is also present in close contact to the vacuole indenting the nucleus of some neurons (arrows), preventing to identify clearly which cell type actually contains the peri-neuronal vacuole. In contrast, immunostaining of Olig2 (H and J) clearly shows that most vacuoles are in close contact to the nucleus of oligodendrocytes in the l2hgdh^-/- mouse brain. Notice the small size of the nucleus of oligodendrocytes compared to the nucleus of neurons. Panels K-N are Transmission Electron Microscopy photographs of striatum tissue. Ultrastructural analysis (K-N) shows many empty-looking cell processes (asterisks in panels M and N), containing dilated cytoplasmic organelles, in the glia of l2hgdh^-/- mice. The myelin sheath of many axons appears focally altered or disrupted (arrows at M and N), sometimes at the vicinity of empty-looking spaces. C, capillary lumen. The length of the scale bar is indicated in each panel.