391 Determining the effects of the pathogenic developmental and epileptic encephalopathy patient variant, SCN1B-p.R98C, on neuronal excitability
Objectives/Goals: Dravet syndrome is a developmental and epileptic encephalopathy associated with refractory seizures and a high risk of sudden unexpected death in epilepsy. A pathogenic biallelic variant in SCN1B, SCN1B-p.R98C, was identified in three patients with Dravet syndrome. Here we investig...
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Cambridge University Press
2025-04-01
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| Series: | Journal of Clinical and Translational Science |
| Online Access: | https://www.cambridge.org/core/product/identifier/S2059866124010112/type/journal_article |
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| author | Amanda Catalfio Daniel T. Kashima Chunling Chen Lori L. Isom |
| author_facet | Amanda Catalfio Daniel T. Kashima Chunling Chen Lori L. Isom |
| author_sort | Amanda Catalfio |
| collection | DOAJ |
| description | Objectives/Goals: Dravet syndrome is a developmental and epileptic encephalopathy associated with refractory seizures and a high risk of sudden unexpected death in epilepsy. A pathogenic biallelic variant in SCN1B, SCN1B-p.R98C, was identified in three patients with Dravet syndrome. Here we investigate SCN1B-p.R98C on neuronal function in vivo. Methods/Study Population: Scn1b-p.R98C mice were previously generated using CRISPR-Cas9 gene editing. Homozygous animals exhibit increased susceptibility to hyperthermia induced seizures at postnatal day (P) 15, 100% expression of spontaneous generalized seizures by P30, and ~20% undergo SUDEP by approximately P60. Here we examined the neuronal phenotype of P17–28 male and female Scn1b-p.R89C mice. We used whole-cell patch clamp electrophysiology approaches to measure effects of the variant on passive membrane properties, intrinsic excitability, and single action potential properties of parvalbumin positive (PV+) interneurons and pyramidal neurons in layers 5/6 of the somatosensory cortex and CA1 region of the hippocampus. Wild-type littermates were used as controls. Results/Anticipated Results: Our results show no differences between genotypes in any measure for somatosensory cortical PV+ interneurons or pyramidal neurons. In the CA1 region of the hippocampus, we found no differences for any measure in PV+ interneurons. In contrast, CA1 pyramidal neurons were hyperexcitable, however, with no changes in passive membrane properties or single action potential properties. Discussion/Significance of Impact: |
| format | Article |
| id | doaj-art-4cc4374b89764525a17c6c9e2e8c8ecc |
| institution | DOAJ |
| issn | 2059-8661 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Cambridge University Press |
| record_format | Article |
| series | Journal of Clinical and Translational Science |
| spelling | doaj-art-4cc4374b89764525a17c6c9e2e8c8ecc2025-08-20T02:40:52ZengCambridge University PressJournal of Clinical and Translational Science2059-86612025-04-01912012010.1017/cts.2024.1011391 Determining the effects of the pathogenic developmental and epileptic encephalopathy patient variant, SCN1B-p.R98C, on neuronal excitabilityAmanda Catalfio0Daniel T. Kashima1Chunling Chen2Lori L. Isom3University of MichiganNorthwestern UniversityUniversity of MichiganUniversity of MichiganObjectives/Goals: Dravet syndrome is a developmental and epileptic encephalopathy associated with refractory seizures and a high risk of sudden unexpected death in epilepsy. A pathogenic biallelic variant in SCN1B, SCN1B-p.R98C, was identified in three patients with Dravet syndrome. Here we investigate SCN1B-p.R98C on neuronal function in vivo. Methods/Study Population: Scn1b-p.R98C mice were previously generated using CRISPR-Cas9 gene editing. Homozygous animals exhibit increased susceptibility to hyperthermia induced seizures at postnatal day (P) 15, 100% expression of spontaneous generalized seizures by P30, and ~20% undergo SUDEP by approximately P60. Here we examined the neuronal phenotype of P17–28 male and female Scn1b-p.R89C mice. We used whole-cell patch clamp electrophysiology approaches to measure effects of the variant on passive membrane properties, intrinsic excitability, and single action potential properties of parvalbumin positive (PV+) interneurons and pyramidal neurons in layers 5/6 of the somatosensory cortex and CA1 region of the hippocampus. Wild-type littermates were used as controls. Results/Anticipated Results: Our results show no differences between genotypes in any measure for somatosensory cortical PV+ interneurons or pyramidal neurons. In the CA1 region of the hippocampus, we found no differences for any measure in PV+ interneurons. In contrast, CA1 pyramidal neurons were hyperexcitable, however, with no changes in passive membrane properties or single action potential properties. Discussion/Significance of Impact: https://www.cambridge.org/core/product/identifier/S2059866124010112/type/journal_article |
| spellingShingle | Amanda Catalfio Daniel T. Kashima Chunling Chen Lori L. Isom 391 Determining the effects of the pathogenic developmental and epileptic encephalopathy patient variant, SCN1B-p.R98C, on neuronal excitability Journal of Clinical and Translational Science |
| title | 391 Determining the effects of the pathogenic developmental and epileptic encephalopathy patient variant, SCN1B-p.R98C, on neuronal excitability |
| title_full | 391 Determining the effects of the pathogenic developmental and epileptic encephalopathy patient variant, SCN1B-p.R98C, on neuronal excitability |
| title_fullStr | 391 Determining the effects of the pathogenic developmental and epileptic encephalopathy patient variant, SCN1B-p.R98C, on neuronal excitability |
| title_full_unstemmed | 391 Determining the effects of the pathogenic developmental and epileptic encephalopathy patient variant, SCN1B-p.R98C, on neuronal excitability |
| title_short | 391 Determining the effects of the pathogenic developmental and epileptic encephalopathy patient variant, SCN1B-p.R98C, on neuronal excitability |
| title_sort | 391 determining the effects of the pathogenic developmental and epileptic encephalopathy patient variant scn1b p r98c on neuronal excitability |
| url | https://www.cambridge.org/core/product/identifier/S2059866124010112/type/journal_article |
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