| http://purl.uniprot.org/citations/32280987 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/32280987 | http://www.w3.org/2000/01/rdf-schema#comment | "Mutations in DEP domain containing 5 (DEPDC5) are increasingly appreciated as one of the most common causes of inherited focal epilepsy. Epilepsies due to DEPDC5 mutations are often associated with brain malformations, tend to be drug-resistant, and have been linked to an increased risk of sudden unexplained death in epilepsy (SUDEP). Generation of epilepsy models to define mechanisms of epileptogenesis remains vital for future therapies. Here, we describe a novel mouse model of Depdc5 deficiency with a severe epilepsy phenotype, generated by conditional deletion of Depdc5 in dorsal telencephalic neuroprogenitor cells. In contrast to control and heterozygous mice, Depdc5-Emx1-Cre conditional knockout (CKO) mice demonstrated macrocephaly, spontaneous seizures and premature death. Consistent with increased mTORC1 activation, targeted neurons were enlarged and both neurons and astrocytes demonstrated increased S6 phosphorylation. Electrophysiologic characterization of miniature inhibitory post-synaptic currents in excitatory neurons was consistent with impaired post-synaptic response to GABAergic input, suggesting a potential mechanism for neuronal hyperexcitability. mTORC1 inhibition with rapamycin significantly improved survival of CKO animals and prevented observed seizures, including for up to 40 days following rapamycin withdrawal. These data not only support a primary role for mTORC1 hyperactivation in epilepsy following homozygous loss of Depdc5, but also suggest a developmental window for treatment which may have a durable benefit for some time even after withdrawal."xsd:string |
| http://purl.uniprot.org/citations/32280987 | http://purl.org/dc/terms/identifier | "doi:10.1093/hmg/ddaa068"xsd:string |
| http://purl.uniprot.org/citations/32280987 | http://purl.uniprot.org/core/author | "Zhou C."xsd:string |
| http://purl.uniprot.org/citations/32280987 | http://purl.uniprot.org/core/author | "Carson R.P."xsd:string |
| http://purl.uniprot.org/citations/32280987 | http://purl.uniprot.org/core/author | "Klofas L.K."xsd:string |
| http://purl.uniprot.org/citations/32280987 | http://purl.uniprot.org/core/author | "Short B.P."xsd:string |
| http://purl.uniprot.org/citations/32280987 | http://purl.uniprot.org/core/date | "2020"xsd:gYear |
| http://purl.uniprot.org/citations/32280987 | http://purl.uniprot.org/core/name | "Hum Mol Genet"xsd:string |
| http://purl.uniprot.org/citations/32280987 | http://purl.uniprot.org/core/pages | "1365-1377"xsd:string |
| http://purl.uniprot.org/citations/32280987 | http://purl.uniprot.org/core/title | "Prevention of premature death and seizures in a Depdc5 mouse epilepsy model through inhibition of mTORC1."xsd:string |
| http://purl.uniprot.org/citations/32280987 | http://purl.uniprot.org/core/volume | "29"xsd:string |
| http://purl.uniprot.org/citations/32280987 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/32280987 |
| http://purl.uniprot.org/citations/32280987 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/32280987 |
| http://purl.uniprot.org/uniprot/#_D3Z7M7-mappedCitation-32280987 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/32280987 |
| http://purl.uniprot.org/uniprot/#_A0A0J9YU49-mappedCitation-32280987 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/32280987 |
| http://purl.uniprot.org/uniprot/#_A0A0J9YV31-mappedCitation-32280987 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/32280987 |
| http://purl.uniprot.org/uniprot/#_P61460-mappedCitation-32280987 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/32280987 |
| http://purl.uniprot.org/uniprot/#_A0A0G2JFM3-mappedCitation-32280987 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/32280987 |
| http://purl.uniprot.org/uniprot/#_A0A571BG14-mappedCitation-32280987 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/32280987 |
| http://purl.uniprot.org/uniprot/#_D3Z419-mappedCitation-32280987 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/32280987 |
| http://purl.uniprot.org/uniprot/#_D3Z5Y4-mappedCitation-32280987 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/32280987 |
| http://purl.uniprot.org/uniprot/#_E9PWF2-mappedCitation-32280987 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/32280987 |
| http://purl.uniprot.org/uniprot/#_E9QAT3-mappedCitation-32280987 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/32280987 |
| http://purl.uniprot.org/uniprot/#_F6TK47-mappedCitation-32280987 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/32280987 |