Differential gene expression in mutant mice overexpressing or deficient in the serotonin transporter: a focus on urocortin 1.
Fabre V., Massart R., Rachalski A., Jennings K., Brass A., Sharp T., Lesch KP., Lanfumey L., Hamon M.
Transcriptome analyses were performed in the anterior raphe area of mutant mice deficient in the serotonin transporter (5-HTT KO) or overexpressing this protein (5-HTT TG), which exhibit opposite changes in anxiety-related behavior. Among genes with altered expression, the gene encoding the neuropeptide urocortin 1 was down-regulated in 5-HTT KO and up-regulated in 5-HTT TG mice. Expression of the gene encoding cocaine-and-amphetamine-related-peptide, which colocalizes with urocortin 1, was also increased in 5-HTT TG mutants. Real-time RT-PCR confirmed these data and immunoautoradiographic labeling showed that parallel changes in neuropeptide levels were confined to the non-preganglionic Edinger-Westphal nucleus. Thus, 5-HTT expression correlates with that of urocortin 1, suggesting that this peptide can be involved in the behavioral changes observed in 5-HTT mutant mice.