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Brain metabolism can profoundly influence neuronal excitability. Mice with genetic deletion or alteration of Bad (BCL-2 agonist of cell death) exhibit altered brain-cell fuel metabolism, accompanied by resistance to acutely induced epileptic seizures; this seizure protection is mediated by ATP-sensitive potassium (KATP) channels. Here we investigated the effect of BAD manipulation on KATP channel activity and excitability in acute brain slices. We found that BAD's influence on neuronal KATP channels was cell-autonomous and directly affected dentate granule neuron (DGN) excitability. To investigate the role of neuronal KATP channels in the anticonvulsant effects of BAD, we imaged calcium during picrotoxin-induced epileptiform activity in entorhinal-hippocampal slices. BAD knockout reduced epileptiform activity, and this effect was lost upon knockout or pharmacological inhibition of KATP channels. Targeted BAD knockout in DGNs alone was sufficient for the antiseizure effect in slices, consistent with a 'dentate gate' function that is reinforced by increased KATP channel activity.
Pubmed ID: 29368690 RIS Download
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Generate, archive, and distribute world-wide up to 12.000 conditional mutations across the mouse genome in mouse embryonic stem (ES) cells and Establish a limited number of mouse mutants from this resource. EUCOMM contributes the largest fraction of conditionally trapped and targeted genes in mouse C57BL/6N embryonic stem (ES) cells to the IKMC. EUCOMM vectors, mutant ES cells and mutant mice are distributed worldwide, enabling functional genomics research in a standardized and cost-effective manner by a much wider biomedical research community than has been possible previously. EUCOMM mutant ES cells and vectors can be obtained from the European Mouse Mutant Cell Repository (EuMMCR). EUCOMM mutant mice are archived and distributed by the European Mouse Mutant Archive (EMMA). Mutagenesis Strategies * Conditional gene trapping - random approach for expressed genes * Conditional targeted trapping - directed approach, used for expressed genes * Conditional gene targeting - directed approach, used for non-expressed genes
View all literature mentionsCommercial vendor and service provider of laboratory reagents and antibodies. Supplier of scientific instrumentation, reagents and consumables, and software services.
View all literature mentionsCenter that produces knockout mice and carries out high-throughput phenotyping of each line in order to determine function of every gene in mouse genome. These mice will be preserved in repositories and made available to scientific community representing valuable resource for basic scientific research as well as generating new models for human diseases.
View all literature mentionsMus musculus with name C57BL/6J from IMSR.
View all literature mentionslaboratory mouse with name C57BL/6N from MGI.
View all literature mentionslaboratory mouse with name BALB/cAnNCrl from MGI.
View all literature mentionsThis unknown targets
View all literature mentionsThis monoclonal targets Bad antibody [Y208]
View all literature mentionsSoftware package as distribution of ImageJ and ImageJ2 together with Java, Java3D and plugins organized into coherent menu structure. Used to assist research in life sciences.
View all literature mentionsMulti paradigm numerical computing environment and fourth generation programming language developed by MathWorks. Allows matrix manipulations, plotting of functions and data, implementation of algorithms, creation of user interfaces, and interfacing with programs written in other languages, including C, C++, Java, Fortran and Python. Used to explore and visualize ideas and collaborate across disciplines including signal and image processing, communications, control systems, and computational finance.
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