Fig. 1

Expression of constitutively active IKK2 in astrocytes causes cerebellar atrophy and ataxia characterized by prominent Purkinje cell loss. a Fast motor coordination is impaired in IKK2-CA mice at the age of 30-34 weeks. Latency to fall off an accelerating rotarod is reduced. Mean values +/- s.e.m.; statistical analysis: 2-way-ANOVA (n = 11–15), p < 0.0001. b Impaired balance/movement precision in IKK2-CA mice at 30–34 weeks as determined by time required to cross a narrow beam, diameter 11/17/28 mm. mean values +/- s.e.m.; statistical analysis: 2-tailed unpaired t-test (n = 11–15), ** p < 0.01; *** p < 0.001. c IKK2-CA expression results in macroscopic cerebellar atrophy at 36 weeks. Scale bar: 1 mm. d Cerebellar atrophy at 50 weeks shown by MRI (sagittal T2*-weighed image at the midline). Arrow: enlarged CSF filled ventricular cavity due to the reduced cerebellar volume. Scale bar: 1 mm. e Variable onset of cerebellar atrophy between 12 and 20 weeks of age and further progression until the age of 82 weeks. Diagram shows maximal rostro-caudal length of the cerebellum (single animals and mean); statistical analysis: 2-tailed Mann-Whitney-test, * p < 0.05; ** p < 0.01; *** p < 0.001. f Histological analysis of the simple lobule reveals loss of Purkinje cells in the IKK2-CA model. Arrowhead: cells in meningeal foldings, arrows: Purkinje cells. Scale bars: 100 μm (left panels); 20 μm (enlargements, right panels). g Time course of Purkinje cell loss in the simple lobule. Quantification from Nissl stainings. Statistical analysis: 2-tailed unpaired t-test, *** p < 0.001, other time points p > 0.05. h Purkinje cell loss in the simple lobule (SL) and the paramedian lobule (PML) at 36 weeks of age; statistical analysis: 2-tailed unpaired t-test (n = 6–8), *** p < 0.001