Tryptophan hydroxylase 2 genotype determines brain serotonin synthesis but not tissue content in C57Bl/6 and BALB/c congenic mice

NEUROSCIENCE LETTERS

卷:481

Article

Zhang, Xiaodong³  Sotnikova, Tatyana D.⁴  Gainetdinov, Raul R.⁴  Caron, Marc G.^1,2 

[1] Duke Univ, Med Ctr, Dept Cell Biol, Durham, NC 27710 USA

[2] Duke Univ, Med Ctr, Dept Neurobiol, Durham, NC 27710 USA

[3] Duke Natl Univ Singapore, Grad Sch Med, Singapore, Singapore

[4] Italian Inst Technol, Dept Neurosci & Brain Technol, I-16163 Genoa, Italy

关键词: Tryptophan hydroxylase 2;    Serotonin;    5-Hydroxyindoleacetic acid;    Mouse strains;    Congenic mice;    Monoamine oxidase;   

DOI  :  10.1016/j.neulet.2010.06.035

来源: Elsevier

【 摘 要 】

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%. Mouse strains expressing the 1473C allele, such as C57Bl/6, have higher 5-HT synthesis rates than strains expressing the 1473G allele, such as BALB/c. Many studies have attributed strain differences to Tph2 genotype without ruling out the potential role of alterations in other genes To test the role of the C1473G polymorphism in strain differences, we generated C57Bl/6 and BALB/c mice congenic for the Tph2 locus. We found that the 1473G allele reduced 5-HT synthesis in C57Bl/6 mice but had no effect on 5-HT tissue content except for a slight reduction (15%) in the frontal cortex In BALB/c mice, the 1473C allele increased 5-HT synthesis but again did not affect 5-HT tissue content. At the same time, 5-hydroxyindoleacetic acid (5-HIAA) was significantly elevated in BALB/c congenic mice In C57Bl/6 mice, there was no effect of genotype on 5-HIAA levels. BALB/c mice had lower expression of monoamine oxidase A and B than C57Bl/6 mice, but there was no effect of Tph2 genotype On the tail suspension test, escitalopram treatment reduced immobility regardless of genotype These data demonstrate that the C1473G polymorphism determines differences in 5-HT synthesis rates among strains but only minimally affects 5-HT tissue levels (C) 2010 Elsevier Ireland Ltd. All rights reserved

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