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Genetic variants in SCN2A, encoding the NaV1.2 voltage-gated sodium channel, are associated with a range of neurodevelopmental disorders with overlapping phenotypes. Some variants fit into a framework wherein gain-of-function missense variants that increase neuronal excitability lead to developmental and epileptic encephalopathy, while loss-of-function variants that reduce neuronal excitability lead to intellectual disability and/or autism spectrum disorder (ASD) with or without co-morbid seizures. One unique case less easily classified using this framework is the de novo missense variant SCN2A-p.K1422E, associated with infant-onset developmental delay, infantile spasms and features of ASD. Prior structure-function studies demonstrated that K1422E substitution alters ion selectivity of NaV1.2, conferring Ca2+ permeability, lowering overall conductance and conferring resistance to tetrodotoxin (TTX). Based on heterologous expression of K1422E, we developed a compartmental neuron model incorporating variant channels that predicted reductions in peak action potential (AP) speed. We generated Scn2aK1422E mice and characterized effects on neurons and neurological/neurobehavioral phenotypes. Cultured cortical neurons from heterozygous Scn2aK1422E/+ mice exhibited lower current density with a TTX-resistant component and reversal potential consistent with mixed ion permeation. Recordings from Scn2aK1442E/+ cortical slices demonstrated impaired AP initiation and larger Ca2+ transients at the axon initial segment during the rising phase of the AP, suggesting complex effects on channel function. Scn2aK1422E/+ mice exhibited rare spontaneous seizures, interictal electroencephalogram abnormalities, altered induced seizure thresholds, reduced anxiety-like behavior and alterations in olfactory-guided social behavior. Overall, Scn2aK1422E/+ mice present with phenotypes similar yet distinct from other Scn2a models, consistent with complex effects of K1422E on NaV1.2 channel function.
Pubmed ID: 35417922
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Non-profit plasmid repository dedicated to helping scientists around the world share high-quality plasmids. Facilitates archiving and distributing DNA-based research reagents and associated data to scientists worldwide. Repository contains over 65,000 plasmids, including special collections on CRISPR, fluorescent proteins, and ready-to-use viral preparations. There is no cost for scientists to deposit plasmids, which saves time and money associated with shipping plasmids themselves. All plasmids are fully sequenced for validation and sequencing data is openly available. We handle the appropriate Material Transfer Agreements (MTA) with institutions, facilitating open exchange and offering intellectual property and liability protection for depositing scientists. Furthermore, we curate free educational resources for the scientific community including a blog, eBooks, video protocols, and detailed molecular biology resources.
View all literature mentionsA national mouse monoclonal antibody generating resource for biochemical and immunohistochemical applications in mammalian brain. NeuroMabs are generated from mice immunized with synthetic and recombinant immunogens corresponding to components of the neuronal proteome as predicted from genomic and other large-scale cloning efforts. Comprehensive biochemical and immunohistochemical analyses of human, primate and non-primate mammalian brain are incorporated into the initial NeuroMab screening procedure. This yields a subset of mouse mAbs that are optimized for use in brain (i.e. NeuroMabs): for immunocytochemical-based imaging studies of protein localization in adult, developing and pathological brain samples, for biochemical analyses of subunit composition and post-translational modifications of native brain proteins, and for proteomic analyses of native brain protein networks. The NeuroMab facility was initially funded with a five-year U24 cooperative grant from NINDS and NIMH. The initial goal of the facility for this funding period is to generate a library of novel NeuroMabs against neuronal proteins, initially focusing on membrane proteins (receptors/channels/transporters), synaptic proteins, other neuronal signaling molecules, and proteins with established links to disease states. The scope of the facility was expanded with supplements from the NIH Blueprint for Neuroscience Research to include neurodevelopmental targets, the NIH Roadmap for Medical Research to include epigenetics targets, and NIH Office of Rare Diseases Research to include rare disease targets. These NeuroMabs will then be produced on a large scale and made available to the neuroscience research community on an inexpensive basis as tissue culture supernatants or purified immunoglobulin by Antibodies Inc. The UC Davis/NIH NeuroMab Facility makes NeuroMabs available directly to end users and is unable to accommodate sales to distributors for third party distribution. Note, NeuroMab antibodies are now offered through antibodiesinc.
View all literature mentionsInteractive Matlab toolbox for processing continuous and event-related EEG, MEG and other electrophysiological data incorporating independent component analysis (ICA), time/frequency analysis, artifact rejection, event-related statistics, and several useful modes of visualization of the averaged and single-trial data. First developed on Matlab 5.3 under Linux, EEGLAB runs on Matlab v5 and higher under Linux, Unix, Windows, and Mac OS X (Matlab 7+ recommended). EEGLAB provides an interactive graphic user interface (GUI) allowing users to flexibly and interactively process their high-density EEG and other dynamic brain data using independent component analysis (ICA) and/or time/frequency analysis (TFA), as well as standard averaging methods. EEGLAB also incorporates extensive tutorial and help windows, plus a command history function that eases users'' transition from GUI-based data exploration to building and running batch or custom data analysis scripts. EEGLAB offers a wealth of methods for visualizing and modeling event-related brain dynamics, both at the level of individual EEGLAB ''datasets'' and/or across a collection of datasets brought together in an EEGLAB ''studyset.'' For experienced Matlab users, EEGLAB offers a structured programming environment for storing, accessing, measuring, manipulating and visualizing event-related EEG data. For creative research programmers and methods developers, EEGLAB offers an extensible, open-source platform through which they can share new methods with the world research community by publishing EEGLAB ''plug-in'' functions that appear automatically in the EEGLAB menu of users who download them. For example, novel EEGLAB plug-ins might be built and released to ''pick peaks'' in ERP or time/frequency results, or to perform specialized import/export, data visualization, or inverse source modeling of EEG, MEG, and/or ECOG data. EEGLAB Features * Graphic user interface * Multiformat data importing * High-density data scrolling * Defined EEG data structure * Open source plug-in facility * Interactive plotting functions * Semi-automated artifact removal * ICA & time/frequency transforms * Many advanced plug-in toolboxes * Event & channel location handling * Forward/inverse head/source modeling
View all literature mentionsCell line HEK293T is a Transformed cell line with a species of origin Homo sapiens (Human)
View all literature mentionsMus musculus with name C57BL/6J from IMSR.
View all literature mentionsThis unknown targets NaV1.6 (SCN8A) Channel
View all literature mentionsThis unknown targets SCN2A (NaV1.2) Channel
View all literature mentionsThis unknown targets SCN1A (NaV1.1) Channel
View all literature mentionsThis unknown targets Rabbit IgG (H+L)
View all literature mentionsThis unknown targets Mouse IgG (H+L)
View all literature mentionsThe SciCrunch Infrastructure was developed as a cooperative data platform to be used by diverse communities in making data more FAIR.
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