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Publication : Serotonin transporter transgenic (SERTcre) mouse line reveals developmental targets of serotonin specific reuptake inhibitors (SSRIs).

First Author  Narboux-Nême N Year  2008
Journal  Neuropharmacology Volume  55
Issue  6 Pages  994-1005
PubMed ID  18789954 Mgi Jnum  J:142523
Mgi Id  MGI:3821657 Doi  10.1016/j.neuropharm.2008.08.020
Citation  Narboux-Neme N, et al. (2008) Serotonin transporter transgenic (SERTcre) mouse line reveals developmental targets of serotonin specific reuptake inhibitors (SSRIs). Neuropharmacology 55(6):994-1005
abstractText  The serotonin transporter gene (SLC6A4; synonyms, SERT, 5-HTT) is expressed much more broadly during development than in adulthood. To obtain a full picture of all sites of SERT expression during development we used a new mouse model where Cre recombinase was inserted into the gene encoding the serotonin transporter. Two reporter mouse lines, ROSA26R and the Tau(mGFP), allowed to map all the cells that express SERT at any point during development. Combined LacZ histochemistry and GFP immunolabelling showed neuronal cell bodies and axon fiber tracts. Earliest recombination in embryos was visible in the periphery in the heart and liver by E10.5 followed by recombination in the brain in raphe serotonergic neurons by E12.5. Further, recombination in non-serotonin neurons was visible in the choroid plexus, roof plate, and neural crest derivatives; by E15.5, recombination was found in the dorsal thalamus, cingulate cortex, CA3 field of the hippocampus, retinal ganglion cells, superior olivary nucleus and cochlear nucleus. Postnatally, SERT mediated recombination was visible in the medial prefrontal cortex and layer VI neurons in the isocortex. Recombined cells were co-labelled with Neu-N, but not with GAD67, and were characterized by long range projections (corpus callosum, fornix, thalamocortical). This fate map of serotonin transporter expressing cells emphasizes the broad expression of SERT in non-serotonin neurons during development and clarifies the localization of SERT expression in the hippocampus and limbic cortex. The identification of targets of SSRIs and serotonin releasers during embryonic and early postnatal life helps understanding the very diverse physiological consequences of administration of these drugs during development.
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