{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T06:36:57Z","timestamp":1790836617497,"version":"4.1.0"},"reference-count":50,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2020,12,12]],"date-time":"2020-12-12T00:00:00Z","timestamp":1607731200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2019R1A2C108414011"],"award-info":[{"award-number":["2019R1A2C108414011"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2019R1A2C108414012"],"award-info":[{"award-number":["2019R1A2C108414012"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["BK21 FOUR project"],"award-info":[{"award-number":["BK21 FOUR project"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>(1) Background: We characterized a novel animal model with obesity-induced constipation because constipation is rarely known in genetically engineered mice (GEM); (2) Methods: The changes in the constipation parameters and mechanisms were analyzed in CRISPR-Cas9-mediated leptin (Lep) knockout (KO) mice from eight to 24 weeks; (3) Results: Significant constipation phenotypes were observed in the Lep KO mice since 16 weeks old. These mice showed a significant decrease in the gastrointestinal motility, mucosal layer thickness and ability for mucin secretion as well as the abnormal ultrastructure of Lieberk\u00fchn crypts in the transverse colon. The density or function of the enteric neurons, intestinal Cajal cells (ICC), smooth muscle cells, and the concentration of gastrointestinal (GI) hormones for the GI motility were remarkably changed in Lep KO mice. The downstream signaling pathway of muscarinic acetylcholine receptors (mAChRs) were activated in Lep KO mice, while the expression of adipogenesis-regulating genes were alternatively reduced in the transverse colon of the same mice; (4) Conclusions: These results provide the first strong evidence that Lep KO mice can represent constipation successfully through dysregulation of the GI motility mediated by myenteric neurons, ICC, and smooth muscle cells in the transverse colon during an abnormal function of the lipid metabolism.<\/jats:p>","DOI":"10.3390\/ijms21249464","type":"journal-article","created":{"date-parts":[[2020,12,13]],"date-time":"2020-12-13T23:39:36Z","timestamp":1607902776000},"page":"9464","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Molecular Characterization of Constipation Disease as Novel Phenotypes in CRISPR-Cas9-Generated Leptin Knockout Mice with Obesity"],"prefix":"10.3390","volume":"21","author":[{"given":"Ji Eun","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Biomaterials Science (BK21 FOUR Program), College of Natural Resources &amp; Life Science, Life and Industry Convergence Research Institute, Laboratory Animal Resources Center, Pusan National University, Miryang 50463, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun Ju","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Biomaterials Science (BK21 FOUR Program), College of Natural Resources &amp; Life Science, Life and Industry Convergence Research Institute, Laboratory Animal Resources Center, Pusan National University, Miryang 50463, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Su Jin","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Biomaterials Science (BK21 FOUR Program), College of Natural Resources &amp; Life Science, Life and Industry Convergence Research Institute, Laboratory Animal Resources Center, Pusan National University, Miryang 50463, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeong Eun","family":"Gong","sequence":"additional","affiliation":[{"name":"Department of Biomaterials Science (BK21 FOUR Program), College of Natural Resources &amp; Life Science, Life and Industry Convergence Research Institute, Laboratory Animal Resources Center, Pusan National University, Miryang 50463, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Lim","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Science, College of Nursing and Healthcare Science, Dong-Eui University, Busan 47340, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6534-9575","authenticated-orcid":false,"given":"Jin Tae","family":"Hong","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Chungbuk National University, Chungju 28160, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5144-1725","authenticated-orcid":false,"given":"Dae Youn","family":"Hwang","sequence":"additional","affiliation":[{"name":"Department of Biomaterials Science (BK21 FOUR Program), College of Natural Resources &amp; Life Science, Life and Industry Convergence Research Institute, Laboratory Animal Resources Center, Pusan National University, Miryang 50463, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,12,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1097\/MOP.0b013e32832ff241","article-title":"Recent advances in chronic constipation","volume":"21","author":"Walia","year":"2009","journal-title":"Curr. 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