Developmental Mechanisms of Epilepsy in Sebaceous Nevus Syndrome Caused by KRAS Mutation
- Title
- Developmental Mechanisms of Epilepsy in Sebaceous Nevus Syndrome Caused by KRAS Mutation
- Authors
- BAEK, SEUNG TAE; 김예은; 이희은; 라종철; 김용석
- Date Issued
- 2021-11-03
- Publisher
- 한국분자세포생물학회
- Abstract
- Sebaceous nevus syndrome (SNS) is caused by somatic gain-of-function mutation of HRAS or KRAS. To examine the pathogenesis of SNS in brain, we generated the disease mouse model by overexpression of KRAS p.G12V in developing cortex using in utero electroporation. This model recapitulated histological manifestations observed in the patient. It showed abnormal neuronal differentiation, migration and neuronal morphogenesis. We investigated neuronal excitability at a cellular level, using patch clamp. Both neurons with and without KRAS p.G12V overexpression showed hyperexcitability. To elucidate the molecular mechanism underlying observed pathological phenotypes, we generated drug-inducible KRAS p.G12V expressing human NPC line using destabilization domain. In this cell line, several pathological phenotypes were rescued by ceasing the expression of KRAS p.G12V at the neuron. Stage-specific modulation of the KRAS variant will allow us to characterize molecular and cellular phenotypes that can be reversed. Taken together, these results indicate pathogenic mechanisms of SNS and suggest the possibility of relieving neurological symptoms in SNS patients by recently developed KRAS inhibitors
- URI
- https://oasis.postech.ac.kr/handle/2014.oak/109751
- Article Type
- Conference
- Citation
- KSMCB 2021, 2021-11-03
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