ArticlePloS one2008
Genetic disruption of both tryptophan hydroxylase genes dramatically reduces serotonin and affects behavior in models sensitive to antidepressants.
Article in PloS one, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 129 papers.
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Who cites it
129 citing papers in PubMed, 253 citations in OpenAlex.
- Serotonin deficiency caused by inactivation of Tph2 in mice leads to widespread sex-dependent changes in cerebral oxidative metabolic activity.Journal of neural transmission (Vienna, Austria : 1996) · 2026Article
- Decoding the serotonin-alcohol crosstalk: the role of central serotonergic dysregulation in alcohol use disorder.Pharmacological reports : PR · 2026Review
- Fe(II) with Tris(1-pyrazolyl)methane Complex Increases Thermal Stability In Vitro and Activity In Vivo of the Mutant 447R Form of Mouse Tryptophan Hydroxylase 2.International journal of molecular sciences · 2026Article
- Associations of genetic polymorphisms with boldness, stress response, and route efficiency in homing pigeons (Columba livia).Physiology & behavior · 2026Article
- Integrative Neuroimmune Role of the Parasympathetic Nervous System, Vagus Nerve and Gut Microbiota in Stress Modulation: A Narrative Review.International journal of molecular sciences · 2025Review
- Iron Ions Increase the Thermal Stability In Vitro and Activity In Vivo of the 447R Mutant Form of Mouse Tryptophan Hydroxylase 2.International journal of molecular sciences · 2025Article
- Tryptophan hydroxylase 2 deficiency alters autism-related behavioural phenotypes in rats.Scientific reports · 2025Article
- Intestinal Epithelial Serotonin as a Novel Target for Treating Disorders of Gut-Brain Interaction and Mood.Gastroenterology · 2025Article
- The C1473G Mutation in the MouseBiomolecules · 2025Article
- Systolic and diastolic dysfunction is exacerbated by age and spinal cord injury in male and female mice with central nervous system serotonin deficiency.The Journal of physiology · 2025Article
- Comparison of the Effects of Tetrahydrobiopterine, L-Tryptophan, and Iron Ions on the Thermal Stability of Wild Type and P447R Mutant Tryptophan Hydroxylase 2.Bulletin of experimental biology and medicine · 2025Article
- Lack of striatal-enriched protein tyrosine phosphatase affected the serotonin system, behavior, and brain morphology in mice.Frontiers in psychiatry · 2025Article
- Socio-affective communication in Tph2-deficient rat pups: communal nesting aggravates growth retardation despite ameliorating maternal affiliation deficits.Molecular autism · 2024Article
- Obstructive Sleep Apnea and Serotoninergic Signalling Pathway: Pathomechanism and Therapeutic Potential.International journal of molecular sciences · 2024Review
- Serotonin reuptake inhibitors improve muscle stem cell function and muscle regeneration in male mice.Nature communications · 2024Article
- Disfunction of dorsal raphe nucleus-hippocampus serotonergic-HTR3 transmission results in anxiety phenotype of Neuroplastin 65-deficient mice.Acta pharmacologica Sinica · 2024Article
- Effect of (R)-2-Amino-6-(1R,2S)-1,2-Dihydroxypropyl)-5,6,7,8-Tetrahydropterin-4(3H)-One and Its Structural Analogues on the Temperature Stability of Tryptophan Hydroxylase 2 with the P447R Mutation.Bulletin of experimental biology and medicine · 2024Article
- Ethanol deprivation and central 5-HT deficiency differentially affect the mRNA editing of the 5-HTPharmacological reports : PR · 2023Article
- In Vitro and In Vivo Chaperone Effect of (R)-2-amino-6-(1R, 2S)-1,2-dihydroxypropyl)-5,6,7,8-tetrahydropterin-4(3H)-one on the C1473G Mutant Tryptophan Hydroxylase 2.Biomolecules · 2023Article
- Molecular signature of excessive female aggression: study of stressed mice with genetic inactivation of neuronal serotonin synthesis.Journal of neural transmission (Vienna, Austria : 1996) · 2023Article
69 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The neurotransmitter serotonin (5-HT) plays an important role in both the peripheral and central nervous systems. The biosynthesis of serotonin is regulated by two rate-limiting enzymes, tryptophan hydroxylase-1 and -2 (TPH1 and TPH2). We used a gene-targeting approach to generate mice with selective and complete elimination of the two known TPH isoforms. This resulted in dramatically reduced central 5-HT levels in Tph2 knockout (TPH2KO) and Tph1/Tph2 double knockout (DKO) mice; and substantially reduced peripheral 5-HT levels in DKO, but not TPH2KO mice. Therefore, differential expression of the two isoforms of TPH was reflected in corresponding depletion of 5-HT content in the brain and periphery. Surprisingly, despite the prominent and evolutionarily ancient role that 5-HT plays in both vertebrate and invertebrate physiology, none of these mutations resulted in an overt phenotype. TPH2KO and DKO mice were viable and normal in appearance. Behavioral alterations in assays with predictive validity for antidepressants were among the very few phenotypes uncovered. These behavioral changes were subtle in the TPH2KO mice; they were enhanced in the DKO mice. Herein, we confirm findings from prior descriptions of TPH1 knockout mice and present the first reported phenotypic evaluations of Tph2 and Tph1/Tph2 knockout mice. The behavioral effects observed in the TPH2 KO and DKO mice strongly confirm the role of 5-HT and its synthetic enzymes in the etiology and treatment of affective disorders.
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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.