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 withi n intron 2 of the gene coding for the serotonin transporter protein 5-HTT h ave been associated with susceptibility to affective disorders. We have clo ned two of these intronic polymorphisms. Stin2.10 and Stin2.12, into an exp ression 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 co nsistent 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 da ta suggest that these polymorphic variable number of tandem repeats regions act as transcriptional regulators and have allele-dependent differential e nhancer-like properties within an area of the hindbrain where the 5-HTT gen e is known to be transcribed at this stage of development.