Early-onset epilepsy and postnatal lethality associated with an editing-deficient GluR-B allele in mice.

Abstract

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.

• Authors: R Brusa, F Zimmermann, D S Koh, D Feldmeyer, P Gass, P H Seeburg, R Sprengel
• Journal: Science (New York, N.Y.) (Science) Vol. 270 Issue 5242 Pg. 1677-80 (Dec 08 1995) ISSN: 0036-8075 [Print] United States
• PMID: 7502080 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• RNA Precursors
• Receptors, AMPA
• Glutamic Acid
• Calcium

Topics

• Alleles
• Animals
• Base Sequence
• Calcium (metabolism)
• Epilepsy (genetics, pathology)
• Gene Targeting
• Glutamic Acid (metabolism)
• Heterozygote
• Hippocampus (pathology)
• In Situ Hybridization
• Male
• Mice
• Mice, Inbred C57BL
• Molecular Sequence Data
• Nerve Degeneration
• Neurons (metabolism)
• Polymerase Chain Reaction
• Purkinje Cells (metabolism)
• Pyramidal Cells (metabolism)
• RNA Editing
• RNA Precursors (genetics, metabolism)
• Receptors, AMPA (chemistry, genetics, metabolism)