Summary
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.
Highlights
Pcdh19-shRNA in utero electroporation of the rat brain mimics EIEE9 mosaic condition
Pcdh19 focal mosaic expression impairs migration in the cortex and hippocampus
Pcdh19-shRNA transfected rats present autism-related behaviors and cognitive deficits
Competing Interest Statement
The authors have declared no competing interest.
