Gene Symbol: Tph2
Description: tryptophan hydroxylase 2
Alias: AU043594, Ntph, tryptophan 5-hydroxylase 2, neuronal tryptophan hydroxylase, tryptophan 5-monooxygenase 2
Species: mouse
Products:     Tph2

Top Publications

  1. Jacob J, Storm R, Castro D, Milton C, Pla P, Guillemot F, et al. Insm1 (IA-1) is an essential component of the regulatory network that specifies monoaminergic neuronal phenotypes in the vertebrate hindbrain. Development. 2009;136:2477-85 pubmed publisher
    ..mutants, but fail to produce serotonin because of a failure to activate expression of tryptophan hydroxylase 2 (Tph2), the key enzyme of serotonin biosynthesis. We find that both Insm1 and Ascl1 coordinately specify Tph2 expression...
  2. Zhang X, Beaulieu J, Sotnikova T, Gainetdinov R, Caron M. Tryptophan hydroxylase-2 controls brain serotonin synthesis. Science. 2004;305:217 pubmed
    Dysregulation of brain serotonin contributes to many psychiatric disorders. Tryptophan hydroxylase-2 (Tph2), rather than Tph1, is preferentially expressed in the brain...
  3. Walther D, Peter J, Bashammakh S, Hörtnagl H, Voits M, Fink H, et al. Synthesis of serotonin by a second tryptophan hydroxylase isoform. Science. 2003;299:76 pubmed
  4. Angoa Perez M, Kane M, Briggs D, Sykes C, Shah M, Francescutti D, et al. Genetic depletion of brain 5HT reveals a common molecular pathway mediating compulsivity and impulsivity. J Neurochem. 2012;121:974-84 pubmed publisher
    ..Mice lacking the gene encoding brain tryptophan hydroxylase 2 (Tph2-/-), the initial and rate-limiting enzyme in the synthesis of serotonin, were tested in numerous behavioral assays ..
  5. Beaulieu J, Zhang X, Rodriguiz R, Sotnikova T, Cools M, Wetsel W, et al. Role of GSK3 beta in behavioral abnormalities induced by serotonin deficiency. Proc Natl Acad Sci U S A. 2008;105:1333-8 pubmed publisher
    ..we generated knockin mice expressing a mutant form of the brain 5-HT synthesis enzyme, tryptophan hydroxylase 2 (Tph2)...
  6. Liu Y, Jiang Y, Si Y, Kim J, Chen Z, Rao Y. Molecular regulation of sexual preference revealed by genetic studies of 5-HT in the brains of male mice. Nature. 2011;472:95-9 pubmed publisher
    ..A role for 5-HT was demonstrated by the phenotype of mice lacking tryptophan hydroxylase 2 (Tph2), which is required for the first step of 5-HT synthesis in the brain...
  7. Cote F, Fligny C, Bayard E, Launay J, Gershon M, Mallet J, et al. Maternal serotonin is crucial for murine embryonic development. Proc Natl Acad Sci U S A. 2007;104:329-34 pubmed
    ..Consideration of the maternal genotype may thus help to clarify the influence of other genes in complex diseases, such as mental illness. ..
  8. Gutknecht L, Araragi N, Merker S, Waider J, Sommerlandt F, Mlinar B, et al. Impacts of brain serotonin deficiency following Tph2 inactivation on development and raphe neuron serotonergic specification. PLoS ONE. 2012;7:e43157 pubmed publisher
    ..with brain-specific 5-HT deficiency resulting from a genetically driven constitutive inactivation of neuronal tryptophan hydroxylase-2 (Tph2)...
  9. Zhang S, Liu Y, Rao Y. Serotonin signaling in the brain of adult female mice is required for sexual preference. Proc Natl Acad Sci U S A. 2013;110:9968-73 pubmed publisher
    ..We demonstrate that a genetic manipulation reverses sexual preference without involving sex hormones. Our results indicate that serotonin controls sexual preference. ..

More Information


  1. Gutknecht L, Waider J, Kraft S, Kriegebaum C, Holtmann B, Reif A, et al. Deficiency of brain 5-HT synthesis but serotonergic neuron formation in Tph2 knockout mice. J Neural Transm (Vienna). 2008;115:1127-32 pubmed publisher
    The relative contribution of the two tryptophan hydroxylase (TPH) isoforms, TPH1 and TPH2, to brain serotonergic system function is controversial...
  2. Narboux Nême N, Angenard G, Mosienko V, Klempin F, Pitychoutis P, Deneris E, et al. Postnatal growth defects in mice with constitutive depletion of central serotonin. ACS Chem Neurosci. 2013;4:171-81 pubmed publisher
    ..over postnatal development showed a delayed maturation of the upper cortical layers in the VMAT2(sert-cre) and Tph2(-/-) mice, but not in the VMAT2(pet1-cre) mice...
  3. Waider J, Proft F, Langlhofer G, Asan E, Lesch K, Gutknecht L. GABA concentration and GABAergic neuron populations in limbic areas are differentially altered by brain serotonin deficiency in Tph2 knockout mice. Histochem Cell Biol. 2013;139:267-81 pubmed publisher
    While tryptophan hydroxylase-2 (Tph2) null mutant (Tph2(-/-)) mice are completely deficient in brain serotonin (5-HT) synthesis, the formation of serotonergic neurons and pathfinding of their projections are not impaired...
  4. Walther D, Bader M. A unique central tryptophan hydroxylase isoform. Biochem Pharmacol. 2003;66:1673-80 pubmed
    ..This led us to the detection of a second TPH gene in the genome of humans, mice, and rats, called TPH2. This gene is predominantly expressed in the brain stem, while the classical TPH gene, now called TPH1, is ..
  5. Liu Z, Zhou J, Li Y, Hu F, Lu Y, Ma M, et al. Dorsal raphe neurons signal reward through 5-HT and glutamate. Neuron. 2014;81:1360-1374 pubmed publisher
    ..These experiments demonstrate the ability of DRN neurons to organize reward behaviors and might provide insights into the underlying mechanisms of learning facilitation and anhedonia treatment. ..
  6. Thomas D, Angoa Perez M, Francescutti Verbeem D, Shah M, Kuhn D. The role of endogenous serotonin in methamphetamine-induced neurotoxicity to dopamine nerve endings of the striatum. J Neurochem. 2010;115:595-605 pubmed publisher
    ..Taken together, the present results indicate that endogenous 5HT does not appear to play a role in METH-induced damage to DA nerve endings of the striatum. ..
  7. Zhao Z, Scott M, Chiechio S, Wang J, Renner K, Gereau R, et al. Lmx1b is required for maintenance of central serotonergic neurons and mice lacking central serotonergic system exhibit normal locomotor activity. J Neurosci. 2006;26:12781-8 pubmed
    ..downregulation of Lmx1b expression, with the exception of serotonin transporter Sert and tryptophan hydroxylase TPH2, whose expression appears to be most sensitive to Lmx1b...
  8. Cheng L, Chen C, Luo P, Tan M, Qiu M, Johnson R, et al. Lmx1b, Pet-1, and Nkx2.2 coordinately specify serotonergic neurotransmitter phenotype. J Neurosci. 2003;23:9961-7 pubmed
    ..2, drives 5-HT differentiation in the dorsal spinal cord. Our studies therefore define a molecular pathway necessary and sufficient to specify the serotonergic neurotransmitter phenotype. ..
  9. Liu C, Maejima T, Wyler S, Casadesus G, Herlitze S, Deneris E. Pet-1 is required across different stages of life to regulate serotonergic function. Nat Neurosci. 2010;13:1190-8 pubmed publisher
    ..These findings indicate that Pet-1 is required across the lifespan of the mouse and that behavioral pathogenesis can result from both developmental and adult-onset alterations in serotonergic transcription. ..
  10. Cote F, Thévenot E, Fligny C, Fromes Y, Darmon M, Ripoche M, et al. Disruption of the nonneuronal tph1 gene demonstrates the importance of peripheral serotonin in cardiac function. Proc Natl Acad Sci U S A. 2003;100:13525-30 pubmed
    ..tryptophan hydroxylase (TPH), is encoded by two genes, the well characterized tph1 gene and a recently identified tph2 gene...
  11. Basu B, Desai R, Balaji J, Chaerkady R, Sriram V, Maiti S, et al. Serotonin in pre-implantation mouse embryos is localized to the mitochondria and can modulate mitochondrial potential. Reproduction. 2008;135:657-69 pubmed publisher
    ..stages for the presence of transcripts of the peripheral and neuronal forms of tryptophan hydroxylase (Tph1 and Tph2 respectively) and the classical serotonin transporter (Slc6a4)...
  12. Kane M, Angoa Peréz M, Briggs D, Sykes C, Francescutti D, Rosenberg D, et al. Mice genetically depleted of brain serotonin display social impairments, communication deficits and repetitive behaviors: possible relevance to autism. PLoS ONE. 2012;7:e48975 pubmed publisher
    ..of autism, we analyzed mice lacking brain serotonin (via a null mutation in the gene for tryptophan hydroxylase 2 (TPH2)) for behaviors that are relevant to this disorder...
  13. Klempin F, Beis D, Mosienko V, Kempermann G, Bader M, Alenina N. Serotonin is required for exercise-induced adult hippocampal neurogenesis. J Neurosci. 2013;33:8270-5 pubmed publisher
    ..Using tryptophan hydroxylase (TPH) 2 deficient (Tph2-deficient) mice that lack brain serotonin, we explored the relationship between serotonin signaling and exercise-..
  14. Alenina N, Kikic D, Todiras M, Mosienko V, Qadri F, Plehm R, et al. Growth retardation and altered autonomic control in mice lacking brain serotonin. Proc Natl Acad Sci U S A. 2009;106:10332-7 pubmed publisher
    Serotonin synthesis in mammals is initiated by 2 distinct tryptophan hydroxylases (TPH), TPH1 and TPH2. By genetically ablating TPH2, we created mice (Tph2(-/-)) that lack serotonin in the central nervous system...
  15. Migliarini S, Pacini G, Pelosi B, Lunardi G, Pasqualetti M. Lack of brain serotonin affects postnatal development and serotonergic neuronal circuitry formation. Mol Psychiatry. 2013;18:1106-18 pubmed publisher
    ..of 5-HT synthesis abrogation on CNS development using a knock-in mouse line in which the tryptophan hydroxylase 2 (Tph2) gene is replaced by the eGFP reporter...
  16. Gutknecht L, Kriegebaum C, Waider J, Schmitt A, Lesch K. Spatio-temporal expression of tryptophan hydroxylase isoforms in murine and human brain: convergent data from Tph2 knockout mice. Eur Neuropsychopharmacol. 2009;19:266-82 pubmed publisher
    ..Here, we report a comprehensive spatio-temporal isoform-specific analysis of TPH1 and TPH2 expression during pre- and postnatal development of mouse brain and in adult human brain...
  17. Kriegebaum C, Song N, Gutknecht L, Huang Y, Schmitt A, Reif A, et al. Brain-specific conditional and time-specific inducible Tph2 knockout mice possess normal serotonergic gene expression in the absence of serotonin during adult life. Neurochem Int. 2010;57:512-7 pubmed publisher
    ..We therefore studied different animal models featuring reduced Tph2 expression to investigate the consequences of impaired brain 5-HT synthesis on neuronal development...
  18. Savelieva K, Zhao S, Pogorelov V, Rajan I, Yang Q, Cullinan E, et al. Genetic disruption of both tryptophan hydroxylase genes dramatically reduces serotonin and affects behavior in models sensitive to antidepressants. PLoS ONE. 2008;3:e3301 pubmed publisher
    ..The biosynthesis of serotonin is regulated by two rate-limiting enzymes, tryptophan hydroxylase-1 and -2 (TPH1 and TPH2)...
  19. Siesser W, Zhang X, Jacobsen J, Sotnikova T, Gainetdinov R, Caron M. Tryptophan hydroxylase 2 genotype determines brain serotonin synthesis but not tissue content in C57Bl/6 and BALB/c congenic mice. Neurosci Lett. 2010;481:6-11 pubmed publisher
    Tryptophan hydroxylase 2 (TPH2) catalyzes the rate-limiting step in the synthesis of brain serotonin (5-HT). In a previous report, a single nucleotide polymorphism in mTph2 (C1473G) reduced 5-HT synthesis by 55%...
  20. Sachs B, Ni J, Caron M. Sex differences in response to chronic mild stress and congenital serotonin deficiency. Psychoneuroendocrinology. 2014;40:123-9 pubmed publisher
    ..Overall, these results highlight the importance of interactions between psychiatric disease risk factors such as sex, chronic stress and congenital 5-HT deficiency in the development of aberrant emotional behavior. ..
  21. Bazovkina D, Tsybko A, Filimonova E, Ilchibaeva T, Naumenko V. [Influence of chronic alcohol treatment on the expression of the Bdnf, Bax, Bcl-xL, and CASP3 genes in the mouse brain: Role of the C1473G polymorphism in the gene encoding tryptophan hydroxylase 2]. Mol Biol (Mosk). 2016;50:302-10 pubmed publisher
    ..Thus, the C1473G polymorphism in the Tph-2 gene considerably influenced the changes in the expression patterns of genes involved in the regulation of neurogenesis and neural apoptosis induced by chronic ethanol treatment. ..
  22. Invernizzi R. Role of TPH-2 in brain function: news from behavioral and pharmacologic studies. J Neurosci Res. 2007;85:3030-5 pubmed
    ..Strain comparison might be a useful strategy to investigate the genotype-dependent alterations of TPH-2. ..
  23. Jia Y, Song N, Mao R, Li J, Zhang Q, Huang Y, et al. Abnormal anxiety- and depression-like behaviors in mice lacking both central serotonergic neurons and pancreatic islet cells. Front Behav Neurosci. 2014;8:325 pubmed publisher
    ..Mice lacking either 5-HT or central serotonergic neurons were generated by conditional deletion of Tph2 or Lmx1b respectively...
  24. Osipova D, Kulikov A, Mekada K, Yoshiki A, Moshkin M, Kotenkova E, et al. Distribution of the C1473G polymorphism in tryptophan hydroxylase 2 gene in laboratory and wild mice. Genes Brain Behav. 2010;9:537-43 pubmed publisher
    ..According to these results, the frequency of the 1473G allele in natural populations does not exceed 0.5%, and the C1473G polymorphism is in fact a rare mutation that is possibly eliminated by the forces of natural selection. ..
  25. Kulikov A, Osipova D, Naumenko V, Terenina E, Mormede P, Popova N. A pharmacological evidence of positive association between mouse intermale aggression and brain serotonin metabolism. Behav Brain Res. 2012;233:113-9 pubmed publisher
    ..aggression was positively associated with activity of the key enzyme of 5-HT synthesis - tryptophan hydroxylase 2 (TPH2) in mouse brain...
  26. Omenetti A, Yang L, Gainetdinov R, Guy C, Choi S, Chen W, et al. Paracrine modulation of cholangiocyte serotonin synthesis orchestrates biliary remodeling in adults. Am J Physiol Gastrointest Liver Physiol. 2011;300:G303-15 pubmed publisher
    ..MF, and tryptophan hydroxylase-2 knockin (TPH2KI) mice with an inactivating mutation of the neuronal tryptophan hydroxylase (TPH) isoform, TPH2, were evaluated...
  27. Ortuño M, Robinson S, Subramanyam P, Paone R, Huang Y, Guo X, et al. Serotonin-reuptake inhibitors act centrally to cause bone loss in mice by counteracting a local anti-resorptive effect. Nat Med. 2016;22:1170-1179 pubmed publisher
    ..Hence, this study identifies a dual mode of action of SSRIs on bone remodeling and suggests a therapeutic strategy to block the deleterious effect on bone homeostasis from their chronic use. ..
  28. Clark J, Flick R, Pai L, Szalayova I, Key S, Conley R, et al. Glucocorticoid modulation of tryptophan hydroxylase-2 protein in raphe nuclei and 5-hydroxytryptophan concentrations in frontal cortex of C57/Bl6 mice. Mol Psychiatry. 2008;13:498-506 pubmed
    ..However, with the recent identification of TPH2, it becomes important to distinguish between regulatory effects on the protein expression and activity of the two ..
  29. Naumenko V, Kondaurova E, Bazovkina D, Tsybko A, Tikhonova M, Kulikov A, et al. Effect of brain-derived neurotrophic factor on behavior and key members of the brain serotonin system in genetically predisposed to behavioral disorders mouse strains. Neuroscience. 2012;214:59-67 pubmed publisher
  30. Kim J, Kim A, Zhao Z, Liu X, Chen Z. Postnatal maintenance of the 5-Ht1a-Pet1 autoregulatory loop by serotonin in the raphe nuclei of the brainstem. Mol Brain. 2014;7:48 pubmed publisher
    ..the transcription factor Pet1 was impaired in the rostral raphe nuclei of mice lacking tryptophan hydroxylase 2 (Tph2) after birth. The downregulation of Pet1 was recapitulated in 5-Ht1a-/- mice...
  31. Wyler S, Donovan L, Yeager M, Deneris E. Pet-1 Controls Tetrahydrobiopterin Pathway and Slc22a3 Transporter Genes in Serotonin Neurons. ACS Chem Neurosci. 2015;6:1198-205 pubmed publisher
    Coordinated serotonin (5-HT) synthesis and reuptake depends on coexpression of Tph2, Aadc (Ddc), and Sert (Slc6a4) in brain 5-HT neurons. However, other gene products play critical roles in brain 5-HT synthesis and transport...
  32. Carli M, Kostoula C, Sacchetti G, Mainolfi P, Anastasia A, Villani C, et al. Tph2 gene deletion enhances amphetamine-induced hypermotility: effect of 5-HT restoration and role of striatal noradrenaline release. J Neurochem. 2015;135:674-85 pubmed publisher
    Variants of tryptophan hydroxylase-2 (Tph2), the gene encoding enzyme responsible for the synthesis of brain serotonin (5-HT), have been associated with neuropsychiatric disorders, substance abuse and addiction...
  33. Lemay F, Doré F, Beaulieu J. Increased ethanol consumption despite taste aversion in mice with a human tryptophan hydroxylase 2 loss of function mutation. Neurosci Lett. 2015;609:194-7 pubmed publisher
    Polymorphisms in the gene encoding the brain serotonin synthesis enzyme Tph2 have been identified in mental illnesses, with co-morbidity of substance use disorder...
  34. Bach H, Arango V, Huang Y, Leong S, Mann J, Underwood M. Neuronal tryptophan hydroxylase expression in BALB/cJ and C57Bl/6J mice. J Neurochem. 2011;118:1067-74 pubmed publisher
    ..mouse strain exhibiting low brain serotonin (5-HT) content and a 5-HT biosynthetic enzyme tryptophan hydroxylase (Tph2) variant reported to have lower catalytic activity compared with other inbred base strains...
  35. Wu Q, Clark M, Palmiter R. Deciphering a neuronal circuit that mediates appetite. Nature. 2012;483:594-7 pubmed publisher
    ..receptor signalling in the NTS by either the chronic administration of ondansetron or the genetic inactivation of Tph2 in caudal serotonergic neurons that project to the NTS protects against starvation when AgRP neurons are ablated...
  36. Baan M, Kibbe C, Bushkofsky J, Harris T, Sherman D, Davis D. Transgenic expression of the human growth hormone minigene promotes pancreatic β-cell proliferation. Am J Physiol Regul Integr Comp Physiol. 2015;309:R788-94 pubmed publisher
    ..receptor, and expression of its downstream targets tryptophan hydroxylase-1 (Tph1), tryptophan hydroxylase-2 (Tph2), and cytokine-inducible SH2 containing protein (Cish) was increased...
  37. Isles A, Hathway G, Humby T, de la Riva C, Kendrick K, Wilkinson L. An mTph2 SNP gives rise to alterations in extracellular 5-HT levels, but not in performance on a delayed-reinforcement task. Eur J Neurosci. 2005;22:997-1000 pubmed
    ..Instead, they indicate that perturbations of the 5-HT system via heritable traits may have differential consequences for qualitatively distinct aspects of impulsive behaviour. ..
  38. Sakowski S, Geddes T, Thomas D, Levi E, Hatfield J, Kuhn D. Differential tissue distribution of tryptophan hydroxylase isoforms 1 and 2 as revealed with monospecific antibodies. Brain Res. 2006;1085:11-8 pubmed be a single-gene product, TPH is now known to exist in two isoforms-TPH1 is found in the pineal and gut, and TPH2 is selectively expressed in brain...
  39. Gutknecht L, Popp S, Waider J, Sommerlandt F, Göppner C, Post A, et al. Interaction of brain 5-HT synthesis deficiency, chronic stress and sex differentially impact emotional behavior in Tph2 knockout mice. Psychopharmacology (Berl). 2015;232:2429-41 pubmed publisher
    ..using a mouse model of brain 5-HT deficiency resulting from targeted inactivation of the tryptophan hydroxylase-2 (Tph2) gene...
  40. Clark J, Pai L, Flick R, Rohrer S. Differential hormonal regulation of tryptophan hydroxylase-2 mRNA in the murine dorsal raphe nucleus. Biol Psychiatry. 2005;57:943-6 pubmed
    Recently a novel tryptophan hydroxylase isoform (TPH2) was identified and shown to be highly expressed in the central nervous system (CNS). Hormonal effects on TPH2 mRNA expression in the rodent dorsal raphe nucleus (DRN) are unknown...
  41. Cervo L, Canetta A, Calcagno E, Burbassi S, Sacchetti G, Caccia S, et al. Genotype-dependent activity of tryptophan hydroxylase-2 determines the response to citalopram in a mouse model of depression. J Neurosci. 2005;25:8165-72 pubmed
    ..Interstrain comparisons could probably be a useful strategy for understanding the mechanisms underlying the response to selective serotonin reuptake inhibitors. ..
  42. Li Z, Caron M, Blakely R, Margolis K, Gershon M. Dependence of serotonergic and other nonadrenergic enteric neurons on norepinephrine transporter expression. J Neurosci. 2010;30:16730-40 pubmed publisher
    ..NET expression is essential for development and/or survival of some (5-HT- and calretinin-expressing), but not all (nNOS-expressing), of these neurons. ..
  43. Mosienko V, Matthes S, Hirth N, Beis D, Flinders M, Bader M, et al. Adaptive changes in serotonin metabolism preserve normal behavior in mice with reduced TPH2 activity. Neuropharmacology. 2014;85:73-80 pubmed publisher
    Polymorphisms in the TPH2 gene coding for the serotonin synthesizing enzyme in the brain are considered as risk factors associated with depression and anxiety in humans...
  44. Kulikov A, Osipova D, Naumenko V, Popova N. Association between Tph2 gene polymorphism, brain tryptophan hydroxylase activity and aggressiveness in mouse strains. Genes Brain Behav. 2005;4:482-5 pubmed
    ..enzyme in the biosynthesis of the neurotransmitter--tryptophan hydroxylase isoform (TPH) 2 encoded by the Tph2 gene. Recently the C1473G single-nucleotide polymorphism in the Tph2 gene was reported...
  45. Calcagno E, Canetta A, Guzzetti S, Cervo L, Invernizzi R. Strain differences in basal and post-citalopram extracellular 5-HT in the mouse medial prefrontal cortex and dorsal hippocampus: relation with tryptophan hydroxylase-2 activity. J Neurochem. 2007;103:1111-20 pubmed
    ..2005), particularly in subjects with low 5-HT synthesis, the contribution of serotonergic and non-serotonergic mechanisms to TRP's effect remains to be elucidated. ..
  46. Gentile M, Nawa Y, Lunardi G, Florio T, Matsui H, Colucci D Amato L. Tryptophan hydroxylase 2 (TPH2) in a neuronal cell line: modulation by cell differentiation and NRSF/rest activity. J Neurochem. 2012;123:963-70 pubmed publisher
    ..Two isoforms of TPH (TPH1 and TPH2) have been identified, with TPH2 almost exclusively expressed in the brain...
  47. Kulikov A, Osipova D, Naumenko V, Popova N. The C1473G polymorphism in the tryptophan hydroxylase-2 gene and intermale aggression in mice. Dokl Biol Sci. 2005;402:208-10 pubmed
  48. Wong P, Sze Y, Gray L, Chang C, Cai S, Zhang X. Early life environmental and pharmacological stressors result in persistent dysregulations of the serotonergic system. Front Behav Neurosci. 2015;9:94 pubmed publisher
    ..applied during early-life or adulthood in wild type (WT) mice and mice with deficient tryptophan hydroxylase 2 (TPH2) function...
  49. WHITNEY M, Shemery A, Yaw A, Donovan L, Glass J, Deneris E. Adult Brain Serotonin Deficiency Causes Hyperactivity, Circadian Disruption, and Elimination of Siestas. J Neurosci. 2016;36:9828-42 pubmed publisher
    ..Cre recombinase (AAV-Cre) into the midbrain/pons of mice carrying a loxP-conditional tryptophan hydroxylase 2 (Tph2) allele...
  50. Wang H, Hughes I, Planer W, Parsadanian A, Grider J, Vohra B, et al. The timing and location of glial cell line-derived neurotrophic factor expression determine enteric nervous system structure and function. J Neurosci. 2010;30:1523-38 pubmed publisher
    ..Thus, changes in GDNF expression can create a wide variety of alterations in ENS structure and function and may in part contribute to human motility disorders. ..
  51. Kirby P, Waters P, Delbridge M, Svartman M, Stewart A, Nagai K, et al. Cloning and mapping of platypus SOX2 and SOX14: insights into SOX group B evolution. Cytogenet Genome Res. 2002;98:96-100 pubmed
    ..The sequence similarity and conserved synteny of these group B genes provide clues to their origin. A simple model of SOX group B gene evolution is proposed. ..
  52. Sakowski S, Geddes T, Kuhn D. Mouse tryptophan hydroxylase isoform 2 and the role of proline 447 in enzyme function. J Neurochem. 2006;96:758-65 pubmed
    ..Isoform 1 (TPH1) is found in the pineal gland and gut, and isoform 2 (TPH2) is selectively expressed in brain...
  53. Jørgensen C, Jacobsen J, Caron M, Klein A, Knudsen G, Mikkelsen J. Cerebral 5-HT2A receptor binding, but not mGluR2, is increased in tryptophan hydroxylase 2 decrease-of-function mice. Neurosci Lett. 2013;555:118-22 pubmed publisher
    Transgenic mice with a knock-in (KI) of a tryptophan hydroxylase 2 (Tph2) R439H mutation, analogous to the Tph2 R441H single-nucleotide polymorphism originally identified in a late life depression cohort, have markedly reduced levels of 5-..
  54. Manceau V, Kremmer E, Nabel E, Maucuer A. The protein kinase KIS impacts gene expression during development and fear conditioning in adult mice. PLoS ONE. 2012;7:e43946 pubmed publisher
    ..This difference suggests that disregulation of gene expression due to KIS inactivation affects specific brain functions. ..
  55. Pelosi B, Pratelli M, Migliarini S, Pacini G, Pasqualetti M. Generation of a Tph2 Conditional Knockout Mouse Line for Time- and Tissue-Specific Depletion of Brain Serotonin. PLoS ONE. 2015;10:e0136422 pubmed publisher
    ..of Tph enzymes, belonging to the family of aromatic amino acid hydroxylases and existing in two isoforms, Tph1 and Tph2, responsible for the production of peripheral and brain serotonin, respectively...
  56. Angoa Perez M, Herrera Mundo N, Kane M, Sykes C, Anneken J, Francescutti D, et al. Brain serotonin signaling does not determine sexual preference in male mice. PLoS ONE. 2015;10:e0118603 pubmed publisher
    ..Presently, mice with a null mutation in the gene for tryptophan hydroxylase 2 (TPH2), which are depleted of brain 5-HT, were tested for sexual preference...
  57. Li Z, CHALAZONITIS A, Huang Y, Mann J, Margolis K, Yang Q, et al. Essential roles of enteric neuronal serotonin in gastrointestinal motility and the development/survival of enteric dopaminergic neurons. J Neurosci. 2011;31:8998-9009 pubmed publisher
    ..5-HT biosynthesis depends on tryptophan hydroxylase 1 (TPH1) in EC cells and on TPH2 in neurons; therefore, mice lacking TPH1 and/or TPH2 distinguish EC-derived from neuronal 5-HT...
  58. Tenner K, Qadri F, Bert B, Voigt J, Bader M. The mTPH2 C1473G single nucleotide polymorphism is not responsible for behavioural differences between mouse strains. Neurosci Lett. 2008;431:21-5 pubmed
    Tryptophan hydroxylase 2 (TPH2) is the rate limiting enzyme of serotonin synthesis in the brain...
  59. Izikki M, Hanoun N, Marcos E, Savale L, Barlier Mur A, Saurini F, et al. Tryptophan hydroxylase 1 knockout and tryptophan hydroxylase 2 polymorphism: effects on hypoxic pulmonary hypertension in mice. Am J Physiol Lung Cell Mol Physiol. 2007;293:L1045-52 pubmed
    ..depends on two rate-limiting tryptophan hydroxylases (Tph): Tph1, which is expressed in peripheral organs, and Tph2, which is expressed in neurons...
  60. Solarewicz J, Angoa Perez M, Kuhn D, Mateika J. The sleep-wake cycle and motor activity, but not temperature, are disrupted over the light-dark cycle in mice genetically depleted of serotonin. Am J Physiol Regul Integr Comp Physiol. 2015;308:R10-7 pubmed publisher
    ..Telemetry transmitters were implanted in 24 wild-type mice (Tph2(+/+)) and 24 mice with a null mutation for tryptophan hydroxylase 2 (Tph2(-/-))...
  61. Angoa Perez M, Kane M, Sykes C, Perrine S, Church M, Kuhn D. Brain serotonin determines maternal behavior and offspring survival. Genes Brain Behav. 2014;13:579-91 pubmed publisher
    ..of serotonin to maternal care, we used mice with a null mutation in the gene for tryptophan hydroxylase-2 (TPH2), which results in a genetic depletion of brain serotonin, and tested them in a wide range of maternal behavior ..
  62. Montalbano A, Waider J, Barbieri M, Baytas O, Lesch K, Corradetti R, et al. Cellular resilience: 5-HT neurons in Tph2(-/-) mice retain normal firing behavior despite the lack of brain 5-HT. Eur Neuropsychopharmacol. 2015;25:2022-35 pubmed publisher
    ..e. tryptophan hydroxylase-2 null mice (Tph2(-/-)) and their littermates, Tph2(+/-) and Tph2(+/+), by using whole-cell patch-clamp recordings in a brainstem ..
  63. Osipova D, Kulikov A, Popova N. C1473G polymorphism in mouse tph2 gene is linked to tryptophan hydroxylase-2 activity in the brain, intermale aggression, and depressive-like behavior in the forced swim test. J Neurosci Res. 2009;87:1168-74 pubmed publisher
    Tryptophan hydroxylase-2 (TPH2) is the rate-limiting enzyme of brain serotonin synthesis. The C1473G polymorphism in the mouse tryptophan hydroxylase-2 gene affects the enzyme's activity...
  64. Carlson K, Whitney M, Gadziola M, Deneris E, Wesson D. Preservation of Essential Odor-Guided Behaviors and Odor-Based Reversal Learning after Targeting Adult Brain Serotonin Synthesis. Eneuro. 2016;3: pubmed
    ..established a conditional genetic approach to specifically target adult brain tryptophan hydroxylase 2 (Tph2), encoding the rate-limiting enzyme in brain 5-HT synthesis, and nearly eliminate 5-HT from the mouse forebrain...
  65. Sachs B, Ni J, Caron M. Brain 5-HT deficiency increases stress vulnerability and impairs antidepressant responses following psychosocial stress. Proc Natl Acad Sci U S A. 2015;112:2557-62 pubmed publisher
    ..This observation provides additional preclinical evidence that inhibiting the LHb might represent a promising alternative therapeutic approach under conditions in which selective 5-HT reuptake inhibitors are ineffective. ..
  66. Flood Z, Engel D, Simon C, Negherbon K, Murphy L, Tamavimok W, et al. Brain growth trajectories in mouse strains with central and peripheral serotonin differences: relevance to autism models. Neuroscience. 2012;210:286-95 pubmed publisher
    ..rate in the central nervous system due to a single-nucleotide polymorphism in the tryptophan hydroxylase 2 (Tph2) gene. The postnatal growth of brain mass was analyzed with mixed-effects models that included litter effects...
  67. Ortíz Alvarado R, Guzmán Quevedo O, Mercado Camargo R, Haertle T, Vignes C, Bolaños Jiménez F. Expression of tryptophan hydroxylase in developing mouse taste papillae. FEBS Lett. 2006;580:5371-6 pubmed
    ..Here, we show by quantitative real time RT-PCR that both isoforms of tryptophan hydroxylase (TPH1 and TPH2), the first and rate limiting enzyme of serotonin (5-HT) synthesis, are expressed in developing circumvallate ..
  68. Mosienko V, Beis D, Pasqualetti M, Waider J, Matthes S, Qadri F, et al. Life without brain serotonin: reevaluation of serotonin function with mice deficient in brain serotonin synthesis. Behav Brain Res. 2015;277:78-88 pubmed publisher
    ..In the following years several research groups have independently generated Tph2-deficient mice...
  69. Lukkes J, Kopelman J, Donner N, Hale M, Lowry C. Development × environment interactions control tph2 mRNA expression. Neuroscience. 2013;237:139-50 pubmed publisher
    ..Among vehicle-treated rats, isolation-reared rats had decreased rodent tryptophan hydroxylase 2 (tph2) mRNA expression in ventral and ventrolateral subdivisions of the DR, a pattern observed previously in a rat model ..
  70. Jacobsen J, Siesser W, Sachs B, Peterson S, Cools M, Setola V, et al. Deficient serotonin neurotransmission and depression-like serotonin biomarker alterations in tryptophan hydroxylase 2 (Tph2) loss-of-function mice. Mol Psychiatry. 2012;17:694-704 pubmed publisher
    ..We employed a naturalistic model of 5-HT deficiency, the tryptophan hydroxylase 2 (Tph2) R439H knockin mouse, to address this question...