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Tryptophan hydroxylase-2 controls brain serotonin synthesis.

Dysregulation of brain serotonin contributes to many psychiatric disorders. Tryptophan hydroxylase-2 (Tph2), rather than Tph1, is preferentially expressed in the brain. We report a functional (C1473G) single-nucleotide polymorphism in mouse Tph2 that results in the substitution of Pro447 with Arg447 and leads to decreased serotonin levels in PC12 cells. Moreover, in BALB/cJ and DBA/2 mice that are homozygous for the 1473G allele, brain serotonin tissue content and synthesis are reduced in comparison to C57Bl/6 and 129X1/SvJ mice that are homozygous for the 1473C allele. Our data provide direct evidence for a fundamental role of Tph2 in brain serotonin synthesis.

Pubmed ID: 15247473


  • Zhang X
  • Beaulieu JM
  • Sotnikova TD
  • Gainetdinov RR
  • Caron MG


Science (New York, N.Y.)

Publication Data

July 9, 2004

Associated Grants

  • Agency: NIMH NIH HHS, Id: MH60451

Mesh Terms

  • Alleles
  • Amino Acid Sequence
  • Animals
  • Brain
  • Brain Stem
  • Corpus Striatum
  • Frontal Lobe
  • Humans
  • Mice
  • Mice, Inbred Strains
  • Molecular Sequence Data
  • PC12 Cells
  • Polymorphism, Single Nucleotide
  • Rats
  • Reverse Transcriptase Polymerase Chain Reaction
  • Serotonin
  • Transfection
  • Tryptophan Hydroxylase