Presence of abnormal microglia (and not absence of mature microglia) drives neuromotor phenotype in Itgb8ΔCNS mice. (A–D) Itgb8ΔCNS pups and controls were identified at birth, randomized to receive either ICD or PLX5622, then evaluated for neuromotor symptoms (A) and associated neuropathology (B–D) 90 d later (P90). Compared with Itgb8ΔCNS mice treated with control drug and littermate control mice treated with either ICD or PLX5622, Itgb8ΔCNS mice treated with PLX5622 had normalization of oligodendrocyte abnormalities (B, MBP staining; C, Olig2/NG2/CC2 staining) and interneuron deficiencies (C, PV/SST staining), but persistence of reactive astrocytes (C, Sox9/GFAP staining). Note overlapping staining of GFAP and MBP in B, which shows normalization of MBP staining despite persistent GFAP staining in Itgb8ΔCNS mice treated with PLX5622. (D) Quantification of cellular phenotypes in Itgb8ΔCNS and control mice treated with either ICD or PLX5622. Bars, 100 µm. Error bars indicate SE. *P < 0.05; **P < 0.005; ***P < 0.0005. Behavioral analysis and cell counting: ANOVA with Tukey’s post hoc test; n = 4 animals. a.u., arbitrary units; PLX, PLX5622.