Dataset Information

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

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/wtCre⁺) 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/wtCre⁺ mice, but not in wild-type mice. Gabrg2^fl/wtCre⁺ 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/wtCre⁺ mice. Furthermore, the latency of temperature- or pentylenetetrazol-induced seizures were significantly decreased in Gabrg2^fl/wtCre⁺ mice compared with wild-type mice. In summary, Gabrg2^fl/wtCre⁺ 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.

SUBMITTER: Li X

PROVIDER: S-EPMC8163876 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature

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

Li Xinxiao X Guo Shengnan S Xu Siying S Chen Zhangping Z Wang Lei L Ding Jiangwei J Huo Junming J Xiao Lifei L He Zhenquan Z Jin Zhe Z Wang Feng F Sun Tao T

Cell death & disease 20210528 6

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<sup>fl/wt</ ...[more]

PMID: 34050134

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Dataset Information

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

Publications

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

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