Abstract
Epileptogenic mechanisms in focal cortical dysplasia (FCD) remain elusive, as no animal models faithfully recapitulate FCD seizures, which have distinct electrographic features and a wide range of semiologies. Given that DEPDC5 plays significant roles in focal epilepsies with FCD, we used in utero electroporation with clustered regularly interspaced short palindromic repeats gene deletion to create focal somatic Depdc5 deletion in the rat embryonic brain. Animals developed spontaneous seizures with focal pathological and electroclinical features highly clinically relevant to FCD IIA, paving the way toward understanding its pathogenesis and developing mechanistic-based therapies. Ann Neurol 2018;83:140-146.
© 2018 American Neurological Association.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Animals, Newborn
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Brain / cytology
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Brain Waves / genetics
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Electroencephalography
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Electroporation
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Embryo, Mammalian
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Epilepsy / genetics*
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Epilepsy / pathology
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Epilepsy / physiopathology*
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Female
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GTPase-Activating Proteins
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Green Fluorescent Proteins / genetics
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Green Fluorescent Proteins / metabolism
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In Vitro Techniques
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Magnetic Resonance Imaging
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Male
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Malformations of Cortical Development, Group I / genetics*
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Malformations of Cortical Development, Group I / pathology
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Malformations of Cortical Development, Group I / physiopathology*
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Neurons / physiology
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Rats
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Repressor Proteins / genetics*
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Repressor Proteins / metabolism
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Ribosomal Protein S6 / metabolism
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Sequence Deletion / genetics*
Substances
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DEPDC5 protein, human
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GTPase-Activating Proteins
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Repressor Proteins
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Ribosomal Protein S6
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enhanced green fluorescent protein
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Green Fluorescent Proteins
Supplementary concepts
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Focal cortical dysplasia of Taylor