Fig. 1: Pcdh19 cKO female mice display mosaic expression of PCDH19 and increased seizure susceptibility. | Molecular Psychiatry

Fig. 1: Pcdh19 cKO female mice display mosaic expression of PCDH19 and increased seizure susceptibility.

From: Neuronal network activity and connectivity are impaired in a conditional knockout mouse model with PCDH19 mosaic expression

Fig. 1

a Schematic representation of Pcdh19 gene targeting strategy (E = exon; SP = signal peptide; EC = extracellular cadherin domain; TM = transmembrane domain; CM = conserved motif; Stop = premature stop codons, NMD = nonsense-mediated decay). b Quantification of Pcdh19 expression in cerebral cortex (upper panel) and hippocampus (lower panel) from adult (P90) Pcdh19 cKO female mice (Pcdh19fl/x Syn1-Cre, Mosaic) compared to controls (Pcdh19fl/x, Ctrl). Pcdh19 mRNA was normalized on actin mRNA level (Cortex: N, Ctrl 8, Mosaic 6; Hippocampus: N, Ctrl 7, Mosaic 7; Student’s t-test, **p < 0.01, ***p < 0.001). c Representative PCDH19 Western blots and relative quantification in cortex (upper panel) and hippocampus (lower panel) from adult (P90-120) mice as in b. PCDH19 expression was normalized on GAPDH (Cortex: N, Ctrl 7, Mosaic 8; Hippocampus: N, Ctrl 8, Mosaic 7; Student’s t-test, *p < 0.05, **p < 0.01). d IF on coronal brain slices from mice as in b at P30 stained for PCDH19 and DAPI. PCDH19 expression is shown in cortex (left panels) and hippocampus (DG, right top panels; CA1, right bottom panels). The inserts show higher magnification images; arrows indicate representative couples of PCDH19-positive (yellow arrows) and -negative (white arrows) neurons. Scale bars, 50 µm. e Growth curve of Pcdh19 cKO mice (Pcdh19fl/x Syn1-Cre, Mosaic) and controls (Pcdh19fl/x, Ctrl) showing mice weight expressed in grams (g, left) or in percentage (normalized on Ctrl, right) (N, Ctrl 22, Mosaic 20; mixed-effects two-way ANOVA and FDR post hoc test, *p < 0.05, **p < 0.01). f Weight gain in mice as in e calculated between consecutive weeks (gain expressed as percentage, left) (N, Ctrl 18, Mosaic 19; mixed-effects two-way ANOVA and FDR post hoc test, **p < 0.01) or between 3 weeks and 3 months of age (gain expressed in grams, right) (N, Ctrl 13, Mosaic 12). g Susceptibility of P26-28 Pcdh19 cKO mice (Pcdh19fl/x Syn1-Cre, Mosaic) and controls (Pcdh19fl/x, Ctrl) to pharmacologically-induced seizures. Left, scale of maximum seizure intensity as a function of time after PTZ injection (N, Ctrl 8, Mosaic 8; two-way ANOVA and FDR post hoc test, *p < 0.05). Right, pie charts showing the percentage of mice reaching a certain convulsive stage within 30 min after PTZ injection (N, Ctrl 8, Mosaic 8). h Latency to tonic-clonic seizures (stage 5) onset in the subgroup of mice as in g that experienced this seizure stage (N, Ctrl 1, Mosaic 6). All data (b–c, e–h) are shown as means ± SEM. See also Supplementary Table 1.

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