PT - JOURNAL ARTICLE AU - Cwetsch, Andrzej W AU - Narducci, Roberto AU - Bolla, Maria AU - Pinto, Bruno AU - Perlini, Laura AU - Bassani, Silvia AU - Passafaro, Maria AU - Cancedda, Laura TI - Mosaic expression of X-linked PCDH19 Protein by <em>in Utero</em> Electroporation in Rats Replicates Human Cortical and Hippocampal Developmental Abnormalities, Associated Core Behaviors Related to Autism, and Cognitive Impairment AID - 10.1101/2020.06.12.145508 DP - 2020 Jan 01 TA - bioRxiv PG - 2020.06.12.145508 4099 - http://biorxiv.org/content/early/2020/06/12/2020.06.12.145508.short 4100 - http://biorxiv.org/content/early/2020/06/12/2020.06.12.145508.full 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.