ArticleMolecular and cellular biology2004
Biochemical and phenotypic abnormalities in kynurenine aminotransferase II-deficient mice.
Article in Molecular and cellular biology, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 81 citations in OpenAlex.
- Neuroactive Kynurenines as Pharmacological Targets: New Experimental Tools and Exciting Therapeutic Opportunities.Pharmacological reviews · 2024Review
- The Biology and Biochemistry of Kynurenic Acid, a Potential Nutraceutical with Multiple Biological Effects.International journal of molecular sciences · 2024Review
- Review
- Kynurenic acid in neurodegenerative disorders-unique neuroprotection or double-edged sword?CNS neuroscience & therapeutics · 2022Review
- Galantamine-Memantine Combination and Kynurenine Pathway Enzyme Inhibitors in the Treatment of Neuropsychiatric Disorders.Complex psychiatry · 2021Review
- Multiple roles of haem in cystathionine β-synthase activity: implications for hemin and other therapies of acute hepatic porphyria.Bioscience reports · 2021Article
- Pro-Inflammatory Cytokines: Potential Links between the Endocannabinoid System and the Kynurenine Pathway in Depression.International journal of molecular sciences · 2021Review
- Blockade of KAT II Facilitates LTP in Kynurenine 3-Monooxygenase Depleted Mice.International journal of tryptophan research : IJTR · 2021Article
- Genetic Underpinnings of Host Manipulation byG3 (Bethesda, Md.) · 2020Article
- The role of kynurenine pathway and kynurenic aminotransferase alleles in postpartum depression following cesarean section in Chinese women.Brain and behavior · 2020Article
- Does kynurenic acid act on nicotinic receptors? An assessment of the evidence.Journal of neurochemistry · 2020Review
- Angiotensin II type 1 receptor blockers decrease kynurenic acid production in rat kidney in vitro.Naunyn-Schmiedeberg's archives of pharmacology · 2019Article
- Assessment of Prenatal Kynurenine Metabolism Using Tissue Slices: Focus on the Neosynthesis of Kynurenic Acid in Mice.Developmental neuroscience · 2019Article
- Deficit, but Not Nondeficit, Schizophrenia Is Characterized by Mucosa-Associated Activation of the Tryptophan Catabolite (TRYCAT) Pathway with Highly Specific Increases in IgA Responses Directed to Picolinic, Xanthurenic, and Quinolinic Acid.Molecular neurobiology · 2018Article
- Quantitative Analysis of Kynurenine Aminotransferase II in the Adult Rat Brain Reveals High Expression in Proliferative Zones and Corpus Callosum.Neuroscience · 2018Article
- Xanthurenic Acid Formation from 3-Hydroxykynurenine in the Mammalian Brain: Neurochemical Characterization and Physiological Effects.Neuroscience · 2017Article
- High resolution crystal structures of human kynurenine aminotransferase-I bound to PLP cofactor, and in complex with aminooxyacetate.Protein science : a publication of the Protein Society · 2017Article
- Elevated kynurenine pathway metabolism during neurodevelopment: Implications for brain and behavior.Neuropharmacology · 2017Review
- Structure of the PLP-Form of the Human Kynurenine Aminotransferase II in a Novel Spacegroup at 1.83 Å Resolution.International journal of molecular sciences · 2016Article
- Kynurenines and Glutamate: Multiple Links and Therapeutic Implications.Advances in pharmacology (San Diego, Calif.) · 2016Review
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
Abstract
Kynurenic acid (KYNA) can act as an endogenous modulator of excitatory neurotransmission and has been implicated in the pathogenesis of several neurological and psychiatric diseases. To evaluate its role in the brain, we disrupted the murine gene for kynurenine aminotransferase II (KAT II), the principal enzyme responsible for the synthesis of KYNA in the rat brain. mKat-2(-/-) mice showed no detectable KAT II mRNA or protein. Total brain KAT activity and KYNA levels were reduced during the first month but returned to normal levels thereafter. In contrast, liver KAT activity and KYNA levels in mKat-2(-/-) mice were decreased by >90% throughout life, though no hepatic abnormalities were observed histologically. KYNA-associated metabolites kynurenine, 3-hydroxykynurenine, and quinolinic acid were unchanged in the brain and liver of knockout mice. mKat-2(-/-) mice began to manifest hyperactivity and abnormal motor coordination at 2 weeks of age but were indistinguishable from wild type after 1 month of age. Golgi staining of cortical and striatal neurons revealed enlarged dendritic spines and a significant increase in spine density in 3-week-old mKat-2(-/-) mice but not in 2-month-old animals. Our results show that gene targeting of mKat-2 in mice leads to early and transitory decreases in brain KAT activity and KYNA levels with commensurate behavioral and neuropathological changes and suggest that compensatory changes or ontogenic expression of another isoform may account for the normalization of KYNA levels in the adult mKat-2(-/-) brain.
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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.