Brain hyperplasia in Chd8 heterozygous and mild hypomorphic mice. a Diagrammatic representation of the Chd8 allele containing the neo cassette between exons 3 and 4. Exon 3 splicing to exon 4 yields a 150 bp product (*) by RT-PCR using primers F and R. Aberrant splicing from exon 3 into the neo cassette yields a 246 bp product (**) with primers F and neo. b Quantitative RT-PCR of Chd8 transcripts in E9.5-E10.5 neocortices of indicated genotypes. c Estimation of CHD8 protein levels in E12.5 neocortices by Western blot. *p < 0.05, **p < 0.01, ***p < 0.001. d High-resolution 7 T structural MRI coronal images of Chd8+/− (n = 12, all males, 22 weeks old) and Chd8neo/neo brains (n = 13, 8 males, 5 females, 16 weeks old), from posterior (top) to anterior (bottom) are shown. Absolute volumetric differences, relative to wildtype controls (n = 30, 26 males, 4 females) are coloured according to the scale on the right. Some regions with enlarged volumes are labeled as follows: NCtx neocortex, EcC ectorhinal cortex, EnC entorhinal cortex, HC hippocampus, Cb cerebellum. e Absolute volumes relative to wildtypes are plotted for whole brain, neocortex and several other brain regions for the different genotypes as indicated. –FDR < 0.15, *FDR < 0.05, **FDR < 0.01. See also Additional file 2: Table S1. MRI data from Chd8+/− and littermate control mice used for comparison are from Suetterlin et al.