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 het eromeric pha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA)-sen sitive glutamate receptor channels impermeable to calcium. The codon f or this arginine is introduced at the precursor messenger RNA (pre-mRN A) stage by site-selective adenosine editing of a glutamine codon. Het erozygous mice engineered by gene targeting to harbor an editing-incom petent GluR-B allele synthesized unedited GluR-B subunits and, in prin cipal neurons and interneurons, expressed AMPA receptors with increase d calcium permeability. These mice developed seizures and died by 3 we eks of age, showing that GluR-B pre-mRNA editing is essential for brai n function.