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.
Zhang
Xiaodong
X
Howard Hughes Medical Institute Laboratory, Department of Cell Biology, and Center for Models of Human Disease, Institute for Genome Sciences and Policy, Box 3287, Duke University Medical Center, Durham, NC 27710, USA.
Beaulieu
Jean-Martin
JM
Sotnikova
Tatyana D
TD
Gainetdinov
Raul R
RR
Caron
Marc G
MG
D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000378:metabolism*; D001933:Brain Stem / Q000378:metabolism; D003342:Corpus Striatum / Q000378:metabolism; D005625:Frontal Lobe / Q000378:metabolism; D006801:Humans; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D016716:PC12 Cells; D020641:Polymorphism, Single Nucleotide; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012701:Serotonin / Q000096:biosynthesis*; D014162:Transfection; D014365:Tryptophan Hydroxylase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
D012701:Serotonin; C487802:Tph2 protein, mouse; D014365:Tryptophan Hydroxylase