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.
Brusa
R
R
Laboratory of Molecular Neuroendocrinology, University of Heidelberg, Germany.
Zimmermann
F
F
Koh
D S
DS
Feldmeyer
D
D
Gass
P
P
Seeburg
P H
PH
Sprengel
R
R
D000483:Alleles; D000818:Animals; D001483:Base Sequence; D002118:Calcium / Q000378:metabolism; D004827:Epilepsy / Q000235:genetics* / Q000473:pathology; D018390:Gene Targeting; D018698:Glutamic Acid / Q000378:metabolism; D006579:Heterozygote; D006624:Hippocampus / Q000473:pathology; D017403:In Situ Hybridization; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009410:Nerve Degeneration; D009474:Neurons / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D011689:Purkinje Cells / Q000378:metabolism; D017966:Pyramidal Cells / Q000378:metabolism; D017393:RNA Editing; D012322:RNA Precursors / Q000235:genetics / Q000378:metabolism; D018091:Receptors, AMPA / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism
D012322:RNA Precursors; D018091:Receptors, AMPA; D018698:Glutamic Acid; D002118:Calcium