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It is abundantly expressed in the gastrointestinal (GI<\/jats:styled-content>) system and is thought to play an important role in GI<\/jats:styled-content> motility, secretion, and visceral sensitivity. Previously, the physiological and pathophysiological functions of Tacr2<\/jats:italic> were mainly studied using Tacr2<\/jats:italic> selective agonists or antagonists. Here, we seek to investigate the effect of Tacr2<\/jats:italic> disruption in mice to provide further insights.<\/jats:p><\/jats:sec>Methods<\/jats:title>The Tacr2<\/jats:italic> knockout mice were generated by homologous recombination and the phenotypic changes of the Tacr2<\/jats:italic>\u2010null mice were analyzed and compared with their wild type (wt) littermates.<\/jats:p><\/jats:sec>Key Results<\/jats:title>Increased food retention was detected in Tacr2<\/jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup> mice. The stomach of Tacr2<\/jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup> mice had thinner muscularis externa and less neurons in the myenteric plexus. The stomach and small intestine exhibited longer duration of electrical field stimulation (EFS<\/jats:styled-content>)\u2010induced inhibition in the gastric fundus and decreased frequency of migrating motor complex (MMC<\/jats:styled-content>), respectively. Neuronal nitric oxide synthase (nNOS) and vasoactive intestinal polypeptide (VIP) were significantly up\u2010regulated due to Tarc2<\/jats:italic> deficiency, contributing to enhanced nitric oxide (NO) signaling in the stomach of Tacr2<\/jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup> mice. Intraperitoneal application of 7\u2010nitroindazole (7\u2010NI<\/jats:styled-content>) to Tacr2<\/jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup> mice effectively relieved the gastric emptying disturbance. Moreover, Creb and NF<\/jats:styled-content>\u2010\u03baB signalings were involved in the regulation of these physiological changes initiated by Tacr2<\/jats:italic> deficiency.<\/jats:p><\/jats:sec>Conclusions & Inferences<\/jats:title>Tacr2<\/jats:italic> negatively regulated the expression of nNOS<\/jats:styled-content> and VIP<\/jats:styled-content> both in vivo and in vitro. Its ablation in mice elevated the expression of nNOS<\/jats:styled-content> and VIP<\/jats:styled-content>, enhanced NO<\/jats:styled-content> signaling and changed the Creb and NF<\/jats:styled-content>\u2010\u03baB signalings, finally leading to the gastric emptying disturbance of Tacr2<\/jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup> mice.<\/jats:p><\/jats:sec>","DOI":"10.1111\/nmo.13117","type":"journal-article","created":{"date-parts":[[2017,6,6]],"date-time":"2017-06-06T08:46:46Z","timestamp":1496738806000},"source":"Crossref","is-referenced-by-count":5,"title":["Ablation of Tacr2<\/i> in mice leads to gastric emptying disturbance"],"prefix":"10.1111","volume":"29","author":[{"given":"Y.\u2010L.","family":"Mao","sequence":"first","affiliation":[{"name":"State Key Laboratory of Medical Genomics Research Center for Experimental Medicine Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (SJTUSM) Shanghai 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