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bioRxiv · 10.1101/2020.06.12.145508

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.

Cwetsch, A. W.·Narducci, R.·Bolla, M.·Pinto, B.·Perlini, L.·Bassani, S.·Passafaro, M.·Cancedda, L.
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Abstract

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 Pcdh19 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.

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Cwetsch, A. W., Narducci, R., Bolla, M., Pinto, B., Perlini, L., Bassani, S., Passafaro, M., Cancedda, L.. 2020-06-12. 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.. https://doi.org/10.1101/2020.06.12.145508

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