ArticleProceedings of the National Academy of Sciences of the United States of America1997
Epilepsy in mice deficient in the 65-kDa isoform of glutamic acid decarboxylase.
Article in Proceedings of the National Academy of Sciences of the United States of America, 1997. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 120 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
120 citing papers in PubMed, 1 synthesis or guideline pooled it, 319 citations in OpenAlex.
- Systematic Review of the Genetics of Sudden Unexpected Death in Epilepsy: Potential Overlap With Sudden Cardiac Death and Arrhythmia-Related Genes.Journal of the American Heart Association · 2020Pooled it
- The Anticonvulsant Effect of Long-Term Valproate Might Be Attributable to Altered Expression of Selected Genes in Mice.International journal of molecular sciences · 2026Article
- Presynaptic Trafficking of Glutamate Decarboxylase Isoforms Is Dispensable for Basal GABAergic Neurotransmission.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026Article
- The complex molecular epileptogenesis landscape of glioblastoma.Cell reports. Medicine · 2024Article
- Neurological Phenotypes in Mouse Models of Mitochondrial Disease and Relevance to Human Neuropathology.International journal of molecular sciences · 2023Review
- Developmental and epileptic encephalopathy 89: A novel bi-allelic variant, molecular dynamics simulation, and a comprehensive clinical and molecular profile.Epilepsia open · 2023Article
- Exposure to Juvenile Stress Induces Epigenetic Alterations in the GABAergic System in Rats.Genes · 2023Article
- A method to estimate the cellular composition of the mouse brain from heterogeneous datasets.PLoS computational biology · 2022Article
- Rodent Models of Audiogenic Epilepsy: Genetic Aspects, Advantages, Current Problems and Perspectives.Biomedicines · 2022Review
- Dendritic Inhibition by Shh Signaling-Dependent Stellate Cell Pool Is Critical for Motor Learning.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2022Article
- Crosstalk Between GABAergic Neurotransmission and Inflammatory Cascades in the Post-ischemic Brain: Relevance for Stroke Recovery.Frontiers in cellular neuroscience · 2022Review
- Single-synapse analyses of Alzheimer's disease implicate pathologic tau, DJ1, CD47, and ApoE.Science advances · 2021Article
- Impact of T cells on neurodegeneration in anti-GAD65 limbic encephalitis.Annals of clinical and translational neurology · 2021Article
- Vitamin B-6-Induced Neuropathy: Exploring the Mechanisms of Pyridoxine Toxicity.Advances in nutrition (Bethesda, Md.) · 2021Review
- Structural Variants Selected during Yak Domestication Inferred from Long-Read Whole-Genome Sequencing.Molecular biology and evolution · 2021Article
- Impact of Dysfunctional Feed-Forward Inhibition on Glutamate Decarboxylase Isoforms and γ-Aminobutyric Acid Transporters.International journal of molecular sciences · 2021Article
- Oligodendroglial GABAergic Signaling: More Than Inhibition!Neuroscience bulletin · 2021Review
- The Role of Phospholipase C in GABAergic Inhibition and Its Relevance to Epilepsy.International journal of molecular sciences · 2021Review
- Genetic deletion of the 67-kDa isoform of glutamate decarboxylase alters conditioned fear behavior in rats.FEBS open bio · 2021Article
- Increased expression of GABABrain communications · 2021Article
60 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
gamma-Aminobutyric acid (GABA), the major inhibitory neurotransmitter in the mammalian brain, is synthesized by two glutamate decarboxylase isoforms, GAD65 and GAD67. The separate role of the two isoforms is unknown, but differences in saturation with cofactor and subcellular localization suggest that GAD65 may provide reserve pools of GABA for regulation of inhibitory neurotransmission. We have disrupted the gene encoding GAD65 and backcrossed the mutation into the C57BL/6 strain of mice. In contrast to GAD67-/- animals, which are born with developmental abnormalities and die shortly after birth, GAD65-/- mice appear normal at birth. Basal GABA levels and holo-GAD activity are normal, but the pyridoxal 5' phosphate-inducible apo-enzyme reservoir is significantly decreased. GAD65-/- mice develop spontaneous seizures that result in increased mortality. Seizures can be precipitated by fear or mild stress. Seizure susceptibility is dramatically increased in GAD65-/- mice backcrossed into a second genetic background, the nonobese diabetic (NOD/LtJ) strain of mice enabling electroencephalogram analysis of the seizures. The generally higher basal brain GABA levels in this backcross are significantly decreased by the GAD65-/- mutation, suggesting that the relative contribution of GABA synthesized by GAD65 to total brain GABA levels is genetically determined. Seizure-associated c-fos-like immunoreactivity reveals the involvement of limbic regions of the brain. These data suggest that GABA synthesized by GAD65 is important in the dynamic regulation of neural network excitability, implicate at least one modifier locus in the NOD/LtJ strain, and present GAD65-/- animals as a model of epilepsy involving GABA-ergic pathways.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.