title: C1473G polymorphism in mouse tryptophan hydroxylase-2 gene in the regulation of the reaction to emotional stress.
abstract: Neurotransmitter serotonin (5-HT) is involved in the regulation of stress response. Tryptophan hydroxylase-2 (TPH2) is the key enzyme of serotonin (5-HT) synthesis in the brain. C1473G polymorphism in Tph2 gene is the main factor defining the enzyme activity in the brain of laboratory mice. The effect of interaction between C1473G polymorphism and 30min restriction stress on the behavior in the open field test, c-Fos gene expression and 5-HT metabolism in the brain in adult male of B6-1473C and B6-1473G congenic mouse lines with high and low TPH2 activity was investigated. A significant effect of genotype x stress interaction on c-Fos mRNA in the hypothalamus (F1,21=10.66, p<0.001) and midbrain (F1,21=9.18, p<0.01) was observed. The stress-induced rise of c-Fos mRNA in these structures is more intensive in B6-1473G than in B6-1473C mice. A marked effect of genotype x stress interaction on 5-HT level in the cortex (F1,18=9.38, p<0.01) and 5-HIAA/5-HT turnover rate in the hypothalamus (F1,18=9.01, p<0.01) was revealed. The restriction significantly decreased 5-HT level in the cortex (p<0.01) and increased 5-HIAA/5-HT rate (p<0.001) in the hypothalamus in B6-1473C mice, but not in B6-1473G mice. The present result is the first experimental evidence that C1473G polymorphism is involved in the regulation of the reaction to emotional stress in mice.
authors.affiliation: Department of Genetic Models of Neuropathologies, Federal Research Center Institute of Cytology and Genetics, Siberian Division of the Russian Academy of Science, Novosibirsk, 630090, Russia. Electronic address: Kata_Yurevna@mail.ru.
authors.forename: Ekaterina Y
authors.initials: EY
authors.lastname: Bazhenova
authors.affiliation: Laboratory of Behavioral Neurogenomics, Federal Research Center Institute of Cytology and Genetics, Siberian Division of the Russian Academy of Science, Novosibirsk, 630090, Russia.
authors.forename: Daria V
authors.initials: DV
authors.lastname: Bazovkina
authors.affiliation: Laboratory of Behavioral Neurogenomics, Federal Research Center Institute of Cytology and Genetics, Siberian Division of the Russian Academy of Science, Novosibirsk, 630090, Russia.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Kulikova
authors.affiliation: Department of Genetic Models of Neuropathologies, Federal Research Center Institute of Cytology and Genetics, Siberian Division of the Russian Academy of Science, Novosibirsk, 630090, Russia.
authors.forename: Dariya V
authors.initials: DV
authors.lastname: Fursenko
authors.affiliation: Department of Genetic Models of Neuropathologies, Federal Research Center Institute of Cytology and Genetics, Siberian Division of the Russian Academy of Science, Novosibirsk, 630090, Russia.
authors.forename: Nikita V
authors.initials: NV
authors.lastname: Khotskin
authors.affiliation: Laboratory of Populational Ethnogenetics, Federal Research Center Institute of Cytology and Genetics, Siberian Division of the Russian Academy of Science, Novosibirsk, 630090, Russia.
authors.forename: Daria V
authors.initials: DV
authors.lastname: Lichman
authors.affiliation: Department of Genetic Models of Neuropathologies, Federal Research Center Institute of Cytology and Genetics, Siberian Division of the Russian Academy of Science, Novosibirsk, 630090, Russia.
authors.forename: Alexander V
authors.initials: AV
authors.lastname: Kulikov
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D005838:Genotype; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D008297:Male; D051379:Mice; D011110:Polymorphism, Genetic; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism; D013315:Stress, Psychological / Q000235:genetics / Q000523:psychology*; D014365:Tryptophan Hydroxylase / Q000235:genetics*
chemical_list: D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; C487802:Tph2 protein, mouse; D014365:Tryptophan Hydroxylase
keywords: C1473G polymorphism; Mice; Serotonin; Stress; Tryptophan hydroxylase-2 gene