A knock-in mouse model for KCNQ2-related epileptic encephalopathy displays spontaneous generalized seizures and cognitive impairment.
KCNQ2
epileptic encephalopathy
mouse model
Journal
Epilepsia
ISSN: 1528-1167
Titre abrégé: Epilepsia
Pays: United States
ID NLM: 2983306R
Informations de publication
Date de publication:
05 2020
05 2020
Historique:
received:
03
12
2019
revised:
09
03
2020
accepted:
09
03
2020
pubmed:
3
4
2020
medline:
1
12
2020
entrez:
3
4
2020
Statut:
ppublish
Résumé
Early onset epileptic encephalopathy with suppression-burst is one of the most severe epilepsy phenotypes in human patients. A significant proportion of cases have a genetic origin, and the most frequently mutated gene is KCNQ2, encoding Kv7.2, a voltage-dependent potassium channel subunit, leading to so-called KCNQ2-related epileptic encephalopathy (KCNQ2-REE). To study the pathophysiology of KCNQ2-REE in detail and to provide a relevant preclinical model, we generated and described a knock-in mouse model carrying the recurrent p.(Thr274Met) variant. We introduced the p.(Thr274Met) variant by homologous recombination in embryonic stem cells, injected into C57Bl/6N blastocysts and implanted in pseudopregnant mice. Mice were then bred with 129Sv Cre-deleter to generate heterozygous mice carrying the p.(Thr274Met), and animals were maintained on the 129Sv genetic background. We studied the development of this new model and performed in vivo electroencephalographic (EEG) recordings, neuroanatomical studies at different time points, and multiple behavioral tests. The Kcnq2 Taken together, our results indicate that we have generated a relevant model to study the pathophysiology of KCNQ2-related epileptic encephalopathy and perform preclinical research for that devastating and currently intractable disease.
Identifiants
pubmed: 32239694
doi: 10.1111/epi.16494
pmc: PMC7317210
doi:
Substances chimiques
KCNQ2 Potassium Channel
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
868-878Subventions
Organisme : ANR
ID : ANR-14-CE13-0011
Pays : International
Organisme : ANR
ID : ANR-19-CE17-0018
Pays : International
Organisme : Fondation JED Belgique
Pays : International
Organisme : Inserm
Pays : International
Organisme : Aix Marseille Université
Pays : International
Informations de copyright
© 2020 The Authors. Epilepsia published by Wiley Periodicals, Inc. on behalf of International League Against Epilepsy.
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