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• W2955867461 endingPage "108315" @default.
• W2955867461 startingPage "108315" @default.
• W2955867461 abstract "Dravet Syndrome (DS) is an epileptic disorder characterized by spontaneous and thermally-induced seizures, hyperactivity, cognitive deficits, autistic-like behaviors, and Sudden Unexpected Death in Epilepsy (SUDEP). DS is caused by de novo loss-of-function mutations in the SCN1A gene. Selective loss of GABAergic interneuron excitability is the primary cause of the disease. Up to 60% of Scn1a+/− mice die from SUDEP before sexual maturity. We used Cre-Lox technology to conditionally delete Scn1a in all epiblast-derived somatic cells by crossing a floxed Scn1a mouse with a mouse expressing Cre under the Meox2 promoter. Parental Scn1a flox (F) mice, parental Meox2 Cre+ mice, and their F/+:Meox2-Cre− offspring were phenotypically normal and did not prematurely die. In contrast, F/+:Meox2-Cre+ offspring recapitulated DS seizure and behavioral phenotypes. Unexpectedly, male F/+:Meox2-Cre+ mice demonstrated impaired social interaction, while females did not. In the previous models, colony maintenance required breeding SUDEP survivors, which greatly increased colony size required to sustain experimental animal production, and raised the concern that surviving breeders have epigenetic traits that impart new phenotypes to their offspring. Our method greatly facilitates breeding, recapitulates DS phenotypes, eliminates concerns about parents that are survivors, and provides initial evidence for unexpected sex-dependent social interaction impairment. We introduce a more efficient mouse model of human DS that demonstrates an efficient breeding strategy free from potential inherited epigenetic changes and reveals an unexpected sex-specific impairment of social interaction in DS. This new model should have great value to investigators of DS." @default.
• W2955867461 created "2019-07-12" @default.
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• W2955867461 date "2019-09-01" @default.
• W2955867461 modified "2023-10-06" @default.
• W2955867461 title "A more efficient conditional mouse model of Dravet syndrome: Implications for epigenetic selection and sex-dependent behaviors" @default.
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• W2955867461 doi "https://doi.org/10.1016/j.jneumeth.2019.108315" @default.
• W2955867461 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6686874" @default.
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