Early-Onset Epilepsy and Postnatal Lethality Associated with an Editing-Deficient GluR-B Allele in Mice

doi:10.1126/science.270.5242.1677

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Neuroscience

Science 8 December 1995:
Vol. 270. no. 5242, pp. 1677 - 1680
DOI: 10.1126/science.270.5242.1677

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Early-Onset Epilepsy and Postnatal Lethality Associated with an Editing-Deficient GluR-B Allele in Mice

Rossella Brusa, Frank Zimmermann, Duk-Su Koh, Dirk Feldmeyer, Peter Gass, Peter H. Seeburg, Rolf Sprengel

The arginine residue at position 586 of the GluR-B subunit renders heteromeric alpha -amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA)-sensitive glutamate receptor channels impermeable to calcium. The codon for this arginine is introduced at the precursor messenger RNA (pre-mRNA) stage by site-selective adenosine editing of a glutamine codon. Heterozygous mice engineered by gene targeting to harbor an editing-incompetent GluR-B allele synthesized unedited GluR-B subunits and, in principal neurons and interneurons, expressed AMPA receptors with increased calcium permeability. These mice developed seizures and died by 3 weeks of age, showing that GluR-B pre-mRNA editing is essential for brain function.

R. Brusa, F. Zimmermann, P. H. Seeburg, R. Sprengel, Laboratory of Molecular Neuroendocrinology, Center for Molecular Biology (ZMBH), University of Heidelberg, Im Neuenheimer Feld 282, D-69120 Heidelberg, Germany.
D.-S. Koh, D. Feldmeyer, B. Sakmann, Max-Planck-Institut für Medizinische Forschung, Abteilung Zellphysiologie, Jahnstrasse 29, D-69120 Heidelberg, Germany.
P. Gass, Institut für Neuropathologie, University of Heidelberg, Im Neuenheimer Feld 220, D-69120 Heidelberg, Germany.