{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T09:31:13Z","timestamp":1786354273714,"version":"build-2736575974"},"reference-count":29,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T00:00:00Z","timestamp":1786320000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002241","name":"Japan Science and Technology Agency (JST) FOREST Program","doi-asserted-by":"publisher","award":["JPMJFR210Y"],"award-info":[{"award-number":["JPMJFR210Y"]}],"id":[{"id":"10.13039\/501100002241","id-type":"DOI","asserted-by":"publisher"}]},{"award":["JPMJFR210Y"],"award-info":[{"award-number":["JPMJFR210Y"]}],"id":[{"id":"https:\/\/ror.org\/00097mb19","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science (JSPS) KAKENHI","doi-asserted-by":"publisher","award":["JP24K22142"],"award-info":[{"award-number":["JP24K22142"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science (JSPS) KAKENHI","doi-asserted-by":"publisher","award":["JP23H02969"],"award-info":[{"award-number":["JP23H02969"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science (JSPS) KAKENHI","doi-asserted-by":"publisher","award":["JP25K02715"],"award-info":[{"award-number":["JP25K02715"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science (JSPS) KAKENHI","doi-asserted-by":"publisher","award":["JP23KJ1292"],"award-info":[{"award-number":["JP23KJ1292"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"award":["JP24K22142"],"award-info":[{"award-number":["JP24K22142"]}],"id":[{"id":"https:\/\/ror.org\/00hhkn466","id-type":"ROR","asserted-by":"publisher"}]},{"award":["JP23H02969"],"award-info":[{"award-number":["JP23H02969"]}],"id":[{"id":"https:\/\/ror.org\/00hhkn466","id-type":"ROR","asserted-by":"publisher"}]},{"award":["JP25K02715"],"award-info":[{"award-number":["JP25K02715"]}],"id":[{"id":"https:\/\/ror.org\/00hhkn466","id-type":"ROR","asserted-by":"publisher"}]},{"award":["JP23KJ1292"],"award-info":[{"award-number":["JP23KJ1292"]}],"id":[{"id":"https:\/\/ror.org\/00hhkn466","id-type":"ROR","asserted-by":"publisher"}]},{"name":"JSPS Research Fellowship for Young Scientists"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Methods Protoc.","MPs"],"abstract":"<jats:p>Pancreatic ductal adenocarcinoma (PDAC) remains a highly lethal malignancy, highlighting the need for reproducible experimental systems that model pancreatic injury and subsequent neoplastic progression. Adult-onset genetically engineered models in which oncogenic Kras and mutant Trp53 are induced in the pancreas provide a relevant platform for studying PDAC pathogenesis, but efficient neoplastic progression often requires concomitant pancreatic injury. Cerulein-induced pancreatitis is widely used to provide an injury-associated inflammatory stimulus that promotes PDAC progression; however, repeated-injection regimens are labor-intensive and increase cumulative handling stress in animals. Here, we describe a dose-optimized, single-dose L-Lysine protocol designed to induce acute pancreatitis and characterize subsequent pancreatic neoplastic progression in adult-onset Kras\/Trp53-driven mice. Tamoxifen-treated Ptf1aCreER\/+; KrasLSL-G12D\/+; Trp53LSL-R172H\/+; Rosa26-RFP mice received a single intraperitoneal injection of L-Lysine, followed by biochemical, histological, and immunohistochemical assessment of pancreatic injury and tumor development. A single 2.0 g\/kg L-Lysine injection induced sublethal acute pancreatitis characterized by increased serum pancreatic enzymes, interstitial edema, inflammatory cell infiltration, acinar cell necrosis, and rapid mitochondrial alterations. During 3\u20136 months of follow-up, mice developed multifocal acinar-to-ductal metaplasia, PanIN lesions, invasive PDAC, and peritoneal dissemination. This protocol provides a simple, synchronized, and less labor-intensive model for studying pancreatic injury and subsequent neoplastic progression in adult-onset Kras\/Trp53-driven mice.<\/jats:p>","DOI":"10.3390\/mps9040116","type":"journal-article","created":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T08:08:53Z","timestamp":1786349333000},"page":"116","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Single-Dose L-Lysine-Induced Pancreatitis Followed by Pancreatic Neoplastic Progression in Adult Kras\/Trp53-Driven Mice"],"prefix":"10.3390","volume":"9","author":[{"given":"Akihiro","family":"Kaneda","sequence":"first","affiliation":[{"name":"Center for iPS Cell Research and Application, Kyoto University, Kyoto 606-8507, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-5241-1731","authenticated-orcid":false,"given":"Masahiro","family":"Yoshida","sequence":"additional","affiliation":[{"name":"Center for iPS Cell Research and Application, Kyoto University, Kyoto 606-8507, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshiya","family":"Kawaguchi","sequence":"additional","affiliation":[{"name":"Center for iPS Cell Research and Application, Kyoto University, Kyoto 606-8507, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4878-2841","authenticated-orcid":false,"given":"Kenichiro","family":"Furuyama","sequence":"additional","affiliation":[{"name":"Center for iPS Cell Research and Application, Kyoto University, Kyoto 606-8507, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1097\/00000478-200105000-00003","article-title":"Pancreatic intraepithelial neoplasia: A new nomenclature and classification system for pancreatic duct lesions","volume":"25","author":"Hruban","year":"2001","journal-title":"Am. 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