Published on Dec. 8, 1995 in Science volume 270(5242).

PubMed ID: 7502080

DOI: 10.1126/science.270.5242.1677

Abstract:

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