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

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.

Pubmed ID: 7502080 RIS Download

Mesh terms: Alleles | Animals | Base Sequence | Calcium | Epilepsy | Gene Targeting | Glutamic Acid | Heterozygote | Hippocampus | In Situ Hybridization | Male | Mice | Mice, Inbred C57BL | Molecular Sequence Data | Nerve Degeneration | Neurons | Polymerase Chain Reaction | Purkinje Cells | Pyramidal Cells | RNA Editing | RNA Precursors | Receptors, AMPA