Fig. 4. Characterisation of pathological features in cerebella En2cre; Pten^LoxP/LoxP mice. (A) Increased cerebellar size expressed as midsagittal area (mm²) in mutant (red bars) versus controls (blue bars). Evaluation of three sections each. Vertical bars indicate s.d. Significance of the size difference: 9 days, P<0.03; 15 days, P<0.02; 51 days, P<0.004; 184 days, P<0.01. (B) Graphic representation of chronic Purkinje cell loss in En2cre; Pten^LoxP/LoxP mice expressed as cells per mm² in midsagittal sections stained for calbindin. Error bars indicate s.d. (C) Abnormal accumulation of neurofilaments in Purkinje cells En2cre; Pten^LoxP/LoxP mice visualised by Bielschowsky silver impregnation. (D) Occasionally, bi-nucleated neurones were encountered (synaptophysin immunostaining). (E,F) Dysplastic astrocytes, revealed by GFAP immunostaining (E) were seen in aged En2cre; Pten^LoxP/LoxP mice and showed heavy accumulation of phospho-AKT (F). (G,H) Oligodendrocytes (visualised by proteolipid protein in situ hybridisation) were mainly confined to the white matter tracts and only occasionally present within the granular or molecular layer in controls (G), while En2cre; Pten^LoxP/LoxP mutant mice (H) showed a random distribution of these cells, which occasionally reached the cerebellar surface. Frequently, oligodendrocytes formed pairs or clusters (inset in H; I). (I,J) In situ hybridisation of metabotropic glutamate receptor 2 (mGluR2) reveals Golgi cells (cerebellum of control mouse, I) and showed abnormal positioning but no depletion throughout lifetime in En2cre; Pten^LoxP/LoxP mutant cerebella (J). Scale bar: 50 µm in C,E; 30 µm in D; 110 µm in F-H; 80 µm in I,J.

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