title: Mice lacking the 65 kDa isoform of glutamic acid decarboxylase (GAD65) maintain normal levels of GAD67 and GABA in their brains but are susceptible to seizures.
abstract: The gene encoding of the 65 kDa isoform of the gamma-aminobutyric acid (GABA)-synthesizing enzyme, glutamic acid decarboxylase (GAD), GAD65, was targeted in mice by homologous recombination. Viable GAD65 -/- mice were obtained with the expected mendelian frequency and displayed no gross morphological defects. Despite the complete loss of GAD65 mRNA and protein in a homozygous mutant, there was no difference in GABA content in the brains of GAD65 +/+, +/-, and -/- mice. As for the other 67 kDa isoform (GAD67), the levels of mRNA and protein were largely unchanged by the GAD65 mutation. General behavior, including locomotor activity and performance in the Morris water maze task, appeared normal, but seizures were more easily induced by picrotoxin and pentylenetetrazol: the latencies to seizures induced by picrotoxin were shorter and the dose of pentylenetetrazol required for induction of seizures was lower.
authors.affiliation: Laboratory of Neurochemistry, National Institute for Physiological Sciences, Myodaiji, Okazaki, Aichi, 444, Japan. obata@nips.ac.jp
authors.forename: H
authors.initials: H
authors.lastname: Asada
authors.forename: Y
authors.initials: Y
authors.lastname: Kawamura
authors.forename: K
authors.initials: K
authors.lastname: Maruyama
authors.forename: H
authors.initials: H
authors.lastname: Kume
authors.forename: R
authors.initials: R
authors.lastname: Ding
authors.forename: F Y
authors.initials: FY
authors.lastname: Ji
authors.forename: N
authors.initials: N
authors.lastname: Kanbara
authors.forename: H
authors.initials: H
authors.lastname: Kuzume
authors.forename: M
authors.initials: M
authors.lastname: Sanbo
authors.forename: T
authors.initials: T
authors.lastname: Yagi
authors.forename: K
authors.initials: K
authors.lastname: Obata
mesh_terms: D000818:Animals; D001921:Brain / Q000502:physiology*; D005968:Glutamate Decarboxylase / Q000172:deficiency*; D007527:Isoenzymes / Q000172:deficiency*; D008124:Locomotion / Q000502:physiology*; D051379:Mice; D008817:Mice, Mutant Strains; D012640:Seizures / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
chemical_list: D007527:Isoenzymes; D005680:gamma-Aminobutyric Acid; D005968:Glutamate Decarboxylase