A serotonin transporter gene intron 2 polymorphic region, correlated with affective disorders, has allele-dependent differential enhancer-like properties in the mouse embryo.
Polymorphic regions consisting of a variable number of tandem repeats within intron 2 of the gene coding for the serotonin transporter protein 5-HTT have been associated with susceptibility to affective disorders. We have cloned two of these intronic polymorphisms, Stin2.10 and Stin2.12, into an expression vector containing a heterologous minimal promoter and the bacterial LacZ reporter gene. These constructs were then used to produce transgenic mice. In embryonic day 10.5 embryos, both Stin2.10 and Stin2.12 produced consistent beta-galactosidase expression in the embryonic midbrain, hindbrain, and spinal cord floor plate. However, we observed that the levels of beta-galactosidase expression produced by both the Stin2.10 and Stin2.12 within the rostral hindbrain differed significantly at embryonic day 10.5. Our data suggest that these polymorphic variable number of tandem repeats regions act as transcriptional regulators and have allele-dependent differential enhancer-like properties within an area of the hindbrain where the 5-HTT gene is known to be transcribed at this stage of development.
MacKenzie
A
A
Department of Veterinary Pathology, Royal (Dick) School of Veterinary Studies, Summerhall, University of Edinburgh, Edinburgh EH9 1QH, Scotland.
Quinn
J
J
D000818:Animals; D002352:Carrier Proteins / Q000235:genetics*; D002490:Central Nervous System / Q000196:embryology*; D004742:Enhancer Elements, Genetic; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D007438:Introns; D008562:Membrane Glycoproteins / Q000235:genetics*; D026901:Membrane Transport Proteins; D008636:Mesencephalon / Q000737:chemistry / Q000196:embryology; D051379:Mice; D008822:Mice, Transgenic; D019964:Mood Disorders / Q000235:genetics*; D009419:Nerve Tissue Proteins; D011110:Polymorphism, Genetic; D012249:Rhombencephalon / Q000737:chemistry / Q000196:embryology; D012701:Serotonin / Q000378:metabolism*; D050486:Serotonin Plasma Membrane Transport Proteins; D020080:Tandem Repeat Sequences; D014018:Tissue Distribution
D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; C493231:Slc6a4 protein, mouse; D012701:Serotonin