Neocortex- and hippocampus-specific deletion of Gabrg2 causes temperature-dependent seizures in mice

• Main Authors: Xinxiao Li, Shengnan Guo, Siying Xu, Zhangping Chen, Lei Wang, Jiangwei Ding, Junming Huo, Lifei Xiao, Zhenquan He, Zhe Jin, Feng Wang, Tao Sun
• Format: Article
• Language: English
• Published: Nature Publishing Group 2021-05-01
• Series: Cell Death and Disease
• Online Access: https://doi.org/10.1038/s41419-021-03846-x

Abstract Mutations in the GABRG2 gene encoding the γ-aminobutyric acid (GABA) A receptor gamma 2 subunit are associated with genetic epilepsy with febrile seizures plus, febrile seizures plus, febrile seizures, and other symptoms of epilepsy. However, the mechanisms underlying Gabrg2-mediated febrile seizures are poorly understood. Here, we used the Cre/loxP system to generate conditional knockout (CKO) mice with deficient Gabrg2 in the hippocampus and neocortex. Heterozygous CKO mice (Gabrg2 fl/wt Cre + ) exhibited temperature-dependent myoclonic jerks, generalised tonic-clonic seizures, increased anxiety-like symptoms, and a predisposition to induce seizures. Cortical electroencephalography showed the hyperexcitability in response to temperature elevation in Gabrg2 fl/wt Cre + mice, but not in wild-type mice. Gabrg2 fl/wt Cre + mice exhibited spontaneous seizures and susceptibility to temperature-induced seizures. Loss of neurons were observed in cortical layers V–VI and hippocampus of Gabrg2 fl/wt Cre + mice. Furthermore, the latency of temperature- or pentylenetetrazol-induced seizures were significantly decreased in Gabrg2 fl/wt Cre + mice compared with wild-type mice. In summary, Gabrg2 fl/wt Cre + mice with Gabrg2 deletion in the neocortex and hippocampus reproduce many features of febrile seizures and therefore provide a novel model to further understand this syndrome at the cellular and molecular level.