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Review
. 2022 Apr 22;22(4):234-240.
doi: 10.1177/15357597221098230. eCollection 2022 Jul-Aug.

Current Review in Basic Science: Animal Models of Focal Cortical Dysplasia and Epilepsy

Affiliations
Review

Current Review in Basic Science: Animal Models of Focal Cortical Dysplasia and Epilepsy

Lena H Nguyen et al. Epilepsy Curr. .

Abstract

Focal cortical dysplasia (FCD) is a malformation of cortical development that is a prevalent cause of intractable epilepsy in children. Of the three FCD subtypes, understanding the etiology and pathogenesis of FCD type II has seen the most progress owing to the recent advances in identifying gene mutations along the mTOR signaling pathway as a frequent cause of this disorder. Accordingly, numerous animal models of FCD type II based on genetic manipulation of the mTOR signaling pathway have emerged to investigate the mechanisms of epileptogenesis and novel therapeutics for epilepsy. These include transgenic and in utero electroporation-based animal models. Here, we review the histopathological and electroclinical features of existing FCD type II animal models and discuss the scientific and technical considerations, clinical applications, and limitations of current models. We also highlight other models of FCD based on early life acquired factors.

Keywords: CRISPR/Cas9; astrocytes; cortical development; cortical lesion; in utero electroporation; malformation of cortical development; pyramidal neurons; seizure; transgenic mice.

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Conflict of interest statement

Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures

Figure 1.
Figure 1.
Animal models of focal cortical dysplasia (FCD) targeting the mTORC1 signaling pathway. The mTORC1 signaling pathway is a key regulator of neuron growth and development. Mutations in genes encoding regulators of the mTORC1 pathway, including MTOR, PIK3CA, PTEN, TSC1, TSC2, RHEB, DEPDC5, NPRL2, and NPRL3 have been identified as a cause of FCD type II. Based on this, many animal models of FCD type II have been developed by genetically targeting various components of the mTORC1 pathway, either through genetic engineering (transgenic mice) or in utero electroporation. Transgenic mice result in diffuse malformation while in utero electroporation-based models result in focal malformation. Both models recapitulate key phenotypes associated with FCD type II, including cortical disorganization, neuronal misplacement, presence of enlarged dysmorphic neurons, and spontaneous seizures.

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