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Series GSE254640 Query DataSets for GSE254640
Status Public on Jul 05, 2024
Title Long-term downregulation of SCN8A in mouse models of developmental and epileptic encephalopathy II
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary De novo mutations of the voltage-gated sodium channel SCN8A cause severe developmental and epileptic encephalopathy (DEE). Since pathogenic variants have gain-of-function effects on SCN8A activity, reduction of SCN8A expression is an effective therapeutic strategy. We previously described an antisense oligonucleotide (ASO) that delays seizure onset in a mouse model of SCN8A-DEE when administered at postnatal day 2. To investigate the potential effectiveness of post-onset ASO treatment, we first examined the extent of differential gene expression in hippocampus during the pre-onset period. Hippocampal single-nucleus RNA-sequencing detected only minor expression changes after the two month pre-seizure period. ASO treatments that were initiated after seizure onset were protective in the Scn8a mutant mice during the 12 month observation period. As an alternative treatment for down-regulation of Scn8a, we administered a single dose of an AAV10 virus expressing Scn8a shRNA. The viral shRNA was protective against seizures and lethality during the 12 month observation period. These data indicate that reduction of SCN8A expression, either by repeated administration of ASO or a single dose of shRNA virus, may be effective for longterm control of SCN8A-DEE.
 
Overall design Nuclei from adult mouse hippocampus were isolated, purified with FACS sorting, and analyzed with single-nucleus RNA-sequencing (10X Genomics 3' gene expression).
 
Contributor(s) Hill SF, Meisler MH
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Submission date Jan 30, 2024
Last update date Jul 06, 2024
Contact name Sophie Hill
E-mail(s) sfhill@umich.edu
Organization name University of Michigan
Department Human Genetics
Lab Meisler Lab
Street address 1241 E. Catherine St
City Ann Arbor
State/province MI
ZIP/Postal code 48109
Country USA
 
Platforms (1)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (3)
GSM8047578 Hippocampus, post-onset 1, snRNAseq
GSM8047579 Hippocampus, post-onset 2, snRNAseq
GSM8047580 Hippocampus, post-onset 3, snRNAseq
Relations
BioProject PRJNA1071179

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Supplementary file Size Download File type/resource
GSE254640_RAW.tar 262.9 Mb (http)(custom) TAR (of MTX, TSV)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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