{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T15:12:20Z","timestamp":1788534740476,"version":"build-2803163510"},"reference-count":31,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2021,4,27]],"date-time":"2021-04-27T00:00:00Z","timestamp":1619481600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Research Foundation","award":["2018R1A1A1A05078158"],"award-info":[{"award-number":["2018R1A1A1A05078158"]}]},{"name":"National Research Foundation","award":["2017M3A9B4061409"],"award-info":[{"award-number":["2017M3A9B4061409"]}]},{"name":"Korea Ministry of Food and Drug Safety","award":["21173MFDS562"],"award-info":[{"award-number":["21173MFDS562"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Neuronal nitric oxide synthase (nNOS) has various roles as a neurotransmitter. However, studies to date have produced insufficient data to fully support the correlation between nNOS and bowel motility. This study aimed to investigate the correlation between nNOS expression and gastrointestinal (GI) tract motility using a stress-induced neonatal maternal separation (NMS) mouse model. In this study, we generated a genetically modified mouse with the HiBiT sequence knock-in into the nNOS gene using CRISPR\/Cas9 for analyzing accurate nNOS expression. nNOS expression was measured in the stomach, small intestine, large intestine, adrenal gland, and hypothalamus tissues after establishing the NMS model. The NMS model exhibited a significant increase in nNOS expression in large intestine, adrenal gland, and hypothalamus. Moreover, a significant positive correlation was observed between whole gastrointestinal transit time and the expression level of nNOS. We reasoned that NMS induced chronic stress and consequent nNOS activation in the hypothalamic-pituitary-adrenal (HPA) axis, and led to an excessive increase in intestinal motility in the lower GI tract. These results demonstrated that HiBiT is a sensitive and valuable tool for analyzing in vivo gene activation, and nNOS could be a biomarker of the HPA axis-linked lower intestinal tract dysfunction.<\/jats:p>","DOI":"10.3390\/cells10051028","type":"journal-article","created":{"date-parts":[[2021,4,27]],"date-time":"2021-04-27T06:19:11Z","timestamp":1619504351000},"page":"1028","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Positive Correlation between nNOS and Stress-Activated Bowel Motility Is Confirmed by In Vivo HiBiT System"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2057-0820","authenticated-orcid":false,"given":"Jeong Pil","family":"Han","sequence":"first","affiliation":[{"name":"Graduate School of International Agricultural Technology and Green, Institute of Green BioScience and Technology, Seoul National University, 1447 Pyeongchang-ro, Daewha, Pyeongchang 25354, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeong Hyeon","family":"Lee","sequence":"additional","affiliation":[{"name":"Graduate School of International Agricultural Technology and Green, Institute of Green BioScience and Technology, Seoul National University, 1447 Pyeongchang-ro, Daewha, Pyeongchang 25354, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geon Seong","family":"Lee","sequence":"additional","affiliation":[{"name":"Graduate School of International Agricultural Technology and Green, Institute of Green BioScience and Technology, Seoul National University, 1447 Pyeongchang-ro, Daewha, Pyeongchang 25354, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6399-6472","authenticated-orcid":false,"given":"Ok Jae","family":"Koo","sequence":"additional","affiliation":[{"name":"Toolgen Inc., Gasan Digital-ro, Geumcheon, Seoul 08594, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9491-5740","authenticated-orcid":false,"given":"Su Cheong","family":"Yeom","sequence":"additional","affiliation":[{"name":"Graduate School of International Agricultural Technology and Green, Institute of Green BioScience and Technology, Seoul National University, 1447 Pyeongchang-ro, Daewha, Pyeongchang 25354, Korea"},{"name":"WCU Biomodulation Major, Department of Agricultural Biotechnology, Seoul National University, 1 Gwanak-ro, Gwanank, Seoul 08826, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,4,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Xue, Q., Yan, Y., Zhang, R., and Xiong, H. 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