ArticleTranslational psychiatry2020
CRISPR/Cas9-engineered Gad1 elimination in rats leads to complex behavioral changes: implications for schizophrenia.
Article in Translational psychiatry, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 25 citations in OpenAlex.
- Targeting beta-2 adrenergic receptor attenuates schizophrenia-like behavioral effects induced by ketamine in mice: cAMP/PKA/BDNF-PEA-3 and RIM-1α signaling pathways involvement.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2026Article
- Unraveling the Genetic and Molecular Architecture of Autism Spectrum Disorder: Implications for Clinical Genetics and Genomic Diagnostics.International journal of molecular sciences · 2026Review
- Article
- GABAergic Signaling Underlying REM Sleep Deprivation-Induced Spatial Working Memory Deficits.Brain and behavior · 2025Article
- Rats show up to 72 h of significant retention for spatial memory in the radial maze.Learning & behavior · 2024Article
- Article
- Beyond the γ-aminobutyric acid hypothesis of schizophrenia.Frontiers in cellular neuroscience · 2023Review
- Peripheral Nerve Injury Induces Changes in the Activity of Inhibitory Interneurons as Visualized in Transgenic GAD1-GCaMP6s Rats.Biosensors · 2022Article
- Abnormal synaptic plasticity and impaired cognition in schizophrenia.World journal of psychiatry · 2022Review
- Recent Advances in the Production of Genome-Edited Rats.International journal of molecular sciences · 2022Review
- Epilepsy and Migraine Shared Genetic and Molecular Mechanisms: Focus on Therapeutic Strategies.Molecular neurobiology · 2021Review
- CRISPR/Cas: a Nobel Prize award-winning precise genome editing technology for gene therapy and crop improvement.Journal of Zhejiang University. Science. B · 2021Review
- Genetic deletion of the 67-kDa isoform of glutamate decarboxylase alters conditioned fear behavior in rats.FEBS open bio · 2021Article
- Insights: fear of GAD.FEBS open bio · 2021Article
- GABAergic System Dysfunction and Challenges in Schizophrenia Research.Frontiers in cell and developmental biology · 2021Review
- Behavioral Consequences of a Combination ofFrontiers in pharmacology · 2021Article
- A Selective Review of the Excitatory-Inhibitory Imbalance in Schizophrenia: Underlying Biology, Genetics, Microcircuits, and Symptoms.Frontiers in cell and developmental biology · 2021Review
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Authors and funding
17 authors at 7 institutions in 1 country.
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Abstract
GABAergic dysfunctions have been implicated in the pathogenesis of schizophrenia, especially the associated cognitive impairments. The GABA synthetic enzyme glutamate decarboxylase 67-kDa isoform (GAD67) encoded by the GAD1 gene is downregulated in the brains of patients with schizophrenia. Furthermore, a patient with schizophrenia harboring a homozygous mutation of GAD1 has recently been discovered. However, it remains unclear whether loss of function of GAD1 leads to the symptoms observed in schizophrenia, including cognitive impairment. One of the obstacles faced in experimental studies to address this issue is the perinatal lethality of Gad1 knockout (KO) mice, which precluded characterization at the adult stage. In the present study, we successfully generated Gad1 KO rats using CRISPR/Cas9 genome editing technology. Surprisingly, 33% of Gad1 KO rats survived to adulthood and could be subjected to further characterization. The GABA concentration in the Gad1 KO cerebrum was reduced to ~52% of the level in wild-type rats. Gad1 KO rats exhibited impairments in both spatial reference and working memory without affecting adult neurogenesis in the hippocampus. In addition, Gad1 KO rats showed a wide range of behavioral alterations, such as enhanced sensitivity to an NMDA receptor antagonist, hypoactivity in a novel environment, and decreased preference for social novelty. Taken together, the results suggest that Gad1 KO rats could provide a novel model covering not only cognitive deficits but also other aspects of the disorder. Furthermore, the present study teaches an important lesson: differences between species should be considered when developing animal models of human diseases.
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