{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T07:10:53Z","timestamp":1790838653759,"version":"4.1.0"},"reference-count":45,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2024,5,22]],"date-time":"2024-05-22T00:00:00Z","timestamp":1716336000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH","award":["AOD22011-001-00000"],"award-info":[{"award-number":["AOD22011-001-00000"]}]},{"name":"NIH","award":["MOA-AI-21002-01"],"award-info":[{"award-number":["MOA-AI-21002-01"]}]},{"name":"NIH","award":["W81XWH22C0047"],"award-info":[{"award-number":["W81XWH22C0047"]}]},{"DOI":"10.13039\/100000005","name":"Department of Defense","doi-asserted-by":"publisher","award":["AOD22011-001-00000"],"award-info":[{"award-number":["AOD22011-001-00000"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000005","name":"Department of Defense","doi-asserted-by":"publisher","award":["MOA-AI-21002-01"],"award-info":[{"award-number":["MOA-AI-21002-01"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000005","name":"Department of Defense","doi-asserted-by":"publisher","award":["W81XWH22C0047"],"award-info":[{"award-number":["W81XWH22C0047"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Organophosphoate (OP) chemicals are known to inhibit the enzyme acetylcholinesterase (AChE). Studying OP poisoning is difficult because common small animal research models have serum carboxylesterase, which contributes to animals\u2019 resistance to OP poisoning. Historically, guinea pigs have been used for this research; however, a novel genetically modified mouse strain (KIKO) was developed with nonfunctional serum carboxylase (Es1 KO) and an altered acetylcholinesterase (AChE) gene, which expresses the amino acid sequence of the human form of the same protein (AChE KI). KIKO mice were injected with 1xLD50 of an OP nerve agent or vehicle control with or without atropine. After one to three minutes, animals were injected with 35 mg\/kg of the currently fielded Reactivator countermeasure for OP poisoning. Postmortem brains were imaged on a Bruker RapifleX ToF\/ToF instrument. Data confirmed the presence of increased acetylcholine in OP-exposed animals, regardless of treatment or atropine status. More interestingly, we detected a small amount of Reactivator within the brain of both exposed and unexposed animals; it is currently debated if reactivators can cross the blood\u2013brain barrier. Further, we were able to simultaneously image acetylcholine, the primary affected neurotransmitter, as well as determine the location of both Reactivator and acetylcholine in the brain. This study, which utilized sensitive MALDI-MSI methods, characterized KIKO mice as a functional model for OP countermeasure development.<\/jats:p>","DOI":"10.3390\/ijms25115624","type":"journal-article","created":{"date-parts":[[2024,5,22]],"date-time":"2024-05-22T10:00:11Z","timestamp":1716372011000},"page":"5624","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Characterization of Humanized Mouse Model of Organophosphate Poisoning and Detection of Countermeasures via MALDI-MSI"],"prefix":"10.3390","volume":"25","author":[{"given":"Caitlin M.","family":"Tressler","sequence":"first","affiliation":[{"name":"The Johns Hopkins University Applied Imaging Mass Spectrometry Core and Service Center, Division of Cancer Imaging Research, The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Wadsworth","sequence":"additional","affiliation":[{"name":"United States Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, Gunpowder, MD 21010, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samantha","family":"Carriero","sequence":"additional","affiliation":[{"name":"United States Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, Gunpowder, MD 21010, USA"},{"name":"Oak Ridge Institute for Science and Education, Oak Ridge, TN 37830, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalie","family":"Dillman","sequence":"additional","affiliation":[{"name":"The Johns Hopkins University Applied Imaging Mass Spectrometry Core and Service Center, Division of Cancer Imaging Research, The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel","family":"Crawford","sequence":"additional","affiliation":[{"name":"The Johns Hopkins University Applied Imaging Mass Spectrometry Core and Service Center, Division of Cancer Imaging Research, The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4297-4597","authenticated-orcid":false,"given":"Tae-Hun","family":"Hahm","sequence":"additional","affiliation":[{"name":"The Johns Hopkins University Applied Imaging Mass Spectrometry Core and Service Center, Division of Cancer Imaging Research, The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristine","family":"Glunde","sequence":"additional","affiliation":[{"name":"The Johns Hopkins University Applied Imaging Mass Spectrometry Core and Service Center, Division of Cancer Imaging Research, The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA"},{"name":"The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA"},{"name":"Department of Biological Chemistry, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1440-2284","authenticated-orcid":false,"given":"C. Linn","family":"Cadieux","sequence":"additional","affiliation":[{"name":"United States Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, Gunpowder, MD 21010, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,5,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.cotox.2021.04.002","article-title":"Mechanisms of organophosphate neurotoxicity","volume":"26","author":"Tsai","year":"2021","journal-title":"Curr. Opin. 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