RT Journal Article SR Electronic T1 Mosaic expression of X-linked PCDH19 Protein by in Utero Electroporation in Rats Replicates Human Cortical and Hippocampal Developmental Abnormalities, Associated Core Behaviors Related to Autism, and Cognitive Impairment JF bioRxiv FD Cold Spring Harbor Laboratory SP 2020.06.12.145508 DO 10.1101/2020.06.12.145508 A1 Cwetsch, Andrzej W A1 Narducci, Roberto A1 Bolla, Maria A1 Pinto, Bruno A1 Perlini, Laura A1 Bassani, Silvia A1 Passafaro, Maria A1 Cancedda, Laura YR 2020 UL http://biorxiv.org/content/early/2020/06/12/2020.06.12.145508.abstract AB PCDH19 gene-related epilepsy or epileptic encephalopathy, early infantile, 9 (EIEE9) is an infantile onset epilepsy syndrome characterized by psychiatric (including autistic) sensory and cognitive impairment of varying degrees. EIEE9 is caused by X-linked PCDH19 protein loss of function. Due to random X-chromosome inactivation, EIEE9-affected females present a mosaic population of healthy and Pcdh19-mutant cells. Unfortunately, no mouse models recapitulate to date both the brain histological and behavioural deficits present in people with EIEE9. Thus, the search for a proper understanding of the disease, and possible future treatment is hampered. By inducing a focal mosaicism of Pdch19 expression using in utero electroporation in rat, we found here that Pcdh19 signaling in specific brain areas is implicated in neuronal migration, as well as in core behaviors related to autism and cognitive function.In Brief Cwetsch et al. report a rat model of focal brain mosaicism of Pcdh19 downregulation induced by in utero electroporation aimed at mimicking the X-linked inheritance pattern of epileptic-encephalopathy-early-infantile-9 (EIEE9) people. Local mosaic of Pcdh19 downregulation resulted in deficits of brain development, as well as autism-related behaviors and reduced cognitive performance.HighlightsPcdh19-shRNA in utero electroporation of the rat brain mimics EIEE9 mosaic conditionPcdh19 focal mosaic expression impairs migration in the cortex and hippocampusPcdh19-shRNA transfected rats present autism-related behaviors and cognitive deficitsCompeting Interest StatementThe authors have declared no competing interest.