The silencer activity of the novel human serotonin transporter linked polymorphic regions.
Enhancer/silencer activity of each allelic variant of the human serotonin transporter linked polymorphic region (5-HTTLPR) including newly found ones was measured in several cell lines including raphe-nucleus-derived RN46A. 5-HTTLR variants ligated in pGL-3 promoter vector increased luciferase activity in COS-7 cells and PC12 cells, where no significant differences among the variants were observed. In RN46 cell lines, however, 5-HTTLPRs decreased luciferase activity to 80-30%, acting as silencers not as enhancers. Some allelic variants (15, 19, 20 and 22) showed even significantly stronger silencer activities than others in RN46A. We also examined relationship between allelic frequencies, the enhancer/silencer activities and incidents of mood disorder. The categorized genotypic or allelic frequencies was not significantly different between the mood disorder and the control. No significant difference was detected either when analyzed by silencer activities of each allelic variant.
Sakai
Kazuo
K
Laboratory of Molecular Pharmacology, Biosignal Research Center, Kobe University, 1-1 Rokko-dai, Nada, Kobe 657-8501, Japan.
Nakamura
Masayuki
M
Ueno
Shu-ichi
S
Sano
Akira
A
Sakai
Norio
N
Shirai
Yasuhito
Y
Saito
Naoaki
N
D000818:Animals; D019556:COS Cells; D002352:Carrier Proteins / Q000235:genetics*; D005787:Gene Frequency; D020868:Gene Silencing / Q000502:physiology*; D017930:Genes, Reporter; D005838:Genotype; D006801:Humans; D008156:Luciferases / Q000235:genetics; D008562:Membrane Glycoproteins / Q000235:genetics*; D026901:Membrane Transport Proteins; D019964:Mood Disorders / Q000235:genetics; D009419:Nerve Tissue Proteins; D009474:Neurons / Q000166:cytology / Q000502:physiology; D016716:PC12 Cells; D011110:Polymorphism, Genetic; D011903:Raphe Nuclei / Q000166:cytology; D051381:Rats; D050486:Serotonin Plasma Membrane Transport Proteins
D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; C493232:Slc6a4 protein, rat; D008156:Luciferases