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Although visceral hypersensitivity (VH) and disturbed gastrointestinal motility are typical pathophysiological features of IBS, the pathological mechanisms underlying this disease remain unclear. Serotonin system abnormalities are considered to play an important role in the pathomechanisms of IBS. Here, we hypothesize that similar alterations, including VH and colonic motility, induced by serotonin transporter (SERT) knockout result from altered serotonin signaling. We sought to determine the molecular mechanism underlying VH and colonic dysmotility induced by SERT knockout. We found that female SERT (\n                    <jats:italic>slc6a4<\/jats:italic>\n                    )\u2010knockout (KO; ie,\n                    <jats:italic>\n                      slc6a4\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    <\/jats:italic>\n                    ) rats exhibited lower pain pressure thresholds (PPTs) than wild\u2010type (WT; ie,\n                    <jats:italic>\n                      slc6a4\n                      <jats:sup>+\/+<\/jats:sup>\n                    <\/jats:italic>\n                    ) rats in response to colorectal distension (CRD). Significantly increased fecal pellet output and reduced concentration of serum tryptophan were observed in the female SERT KO rats. The concentrations of 5\u2010hydroxytryptamine (5\u2010HT) in platelet\u2010rich plasma (PRP) and serum in SERT KO rats were lower than those in WT rats, but the numbers of enterochromaffin cells (ECs) and the concentrations of 5\u2010HT in colon of SERT KO rats were higher than those of WT rats. Finally, increased expression levels of 5\u2010HT\n                    <jats:sub>1B<\/jats:sub>\n                    receptors, 5\u2010HT\n                    <jats:sub>2C<\/jats:sub>\n                    receptors, 5\u2010HT\n                    <jats:sub>3A<\/jats:sub>\n                    receptors, 5\u2010HT\n                    <jats:sub>3B<\/jats:sub>\n                    receptors, 5\u2010HT\n                    <jats:sub>6<\/jats:sub>\n                    receptors, 5\u2010HT\n                    <jats:sub>7<\/jats:sub>\n                    receptors, and glycosylated dopamine transporters (DATs) were found in the female SERT KO rats. We concluded that alterations in the serotonin system induced by the knockout of slc6a4 might result in VH and accelerated gastrointestinal motility in female SERT KO rats, which can be used as an animal model of IBS.\n                  <\/jats:p>","DOI":"10.1096\/fj.202000007rrr","type":"journal-article","created":{"date-parts":[[2021,6,18]],"date-time":"2021-06-18T10:02:46Z","timestamp":1624010566000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Female serotonin transporter\u2010knockout rat: A potential model of irritable bowel syndrome"],"prefix":"10.1096","volume":"35","author":[{"given":"Zijuan","family":"Bi","sequence":"first","affiliation":[{"name":"Institute of Digestive Diseases, Longhua Hospital Shanghai University of Traditional Chinese Medicine Shanghai 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