{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T07:26:09Z","timestamp":1791012369734,"version":"4.1.0"},"reference-count":55,"publisher":"American Diabetes Association","issue":"1","content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2008,1,1]]},"abstract":"<jats:p>OBJECTIVE\u2014 12\/15-lipoxygenase (12\/15-LO), one of a family of fatty acid oxidoreductase enzymes, reacts with polyenoic fatty acids to produce proinflammatory lipids. 12\/15-LO is expressed in macrophages and pancreatic \u03b2-cells. It enhances interleukin 12 production by macrophages, and several of its products induce apoptosis of \u03b2-cells at nanomolar concentrations in vitro. We had previously demonstrated a role for 12\/15-LO in \u03b2-cell damage in the streptozotocin model of diabetes. Since the gene encoding 12\/15-LO (gene designation Alox15) lies within the Idd4 diabetes susceptibility interval in NOD mice, we hypothesized that 12\/15-LO is also a key regulator of diabetes susceptibility in the NOD mouse.<\/jats:p>\n               <jats:p>RESEARCH DESIGN AND METHODS\u2014 We developed NOD mice carrying an inactivated 12\/15-LO locus (NOD-Alox15null) using a \u201cspeed congenic\u201d protocol, and the mice were monitored for development of insulitis and diabetes.<\/jats:p>\n               <jats:p>RESULTS\u2014 NOD mice deficient in 12\/15-LO develop diabetes at a markedly reduced rate compared with NOD mice (2.5 vs. &amp;gt;60% in females by 30 weeks). Nondiabetic female NOD-Alox15null mice demonstrate improved glucose tolerance, as well as significantly reduced severity of insulitis and improved \u03b2-cell mass, when compared with age-matched nondiabetic NOD females. Disease resistance is associated with decreased numbers of islet-infiltrating activated macrophages at 4 weeks of age in NOD-Alox15null mice, preceding the development of insulitis. Subsequently, islet-associated infiltrates are characterized by decreased numbers of CD4+ T cells and increased Foxp3+ cells.<\/jats:p>\n               <jats:p>CONCLUSIONS\u2014 These results suggest an important role for 12\/15-LO in conferring susceptibility to autoimmune diabetes in NOD mice through its effects on macrophage recruitment or activation.<\/jats:p>","DOI":"10.2337\/db07-0830","type":"journal-article","created":{"date-parts":[[2007,10,17]],"date-time":"2007-10-17T03:19:44Z","timestamp":1192591184000},"page":"199-208","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":85,"title":["Nonobese Diabetic (NOD) Mice Congenic for a Targeted Deletion of 12\/15-Lipoxygenase Are Protected From Autoimmune Diabetes"],"prefix":"10.2337","volume":"57","author":[{"given":"Marcia","family":"McDuffie","sequence":"first","affiliation":[{"name":"From the University of Virginia, Charlottesville, Virginia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nelly A.","family":"Maybee","sequence":"additional","affiliation":[{"name":"From the University of Virginia, Charlottesville, Virginia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanna R.","family":"Keller","sequence":"additional","affiliation":[{"name":"From the University of Virginia, Charlottesville, Virginia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian K.","family":"Stevens","sequence":"additional","affiliation":[{"name":"From the University of Virginia, Charlottesville, Virginia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James C.","family":"Garmey","sequence":"additional","affiliation":[{"name":"From the University of Virginia, Charlottesville, Virginia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret A.","family":"Morris","sequence":"additional","affiliation":[{"name":"From the University of Virginia, Charlottesville, Virginia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Kropf","sequence":"additional","affiliation":[{"name":"From the University of Virginia, Charlottesville, Virginia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Rival","sequence":"additional","affiliation":[{"name":"From the University of Virginia, Charlottesville, Virginia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaiwen","family":"Ma","sequence":"additional","affiliation":[{"name":"From the University of Virginia, Charlottesville, Virginia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey D.","family":"Carter","sequence":"additional","affiliation":[{"name":"From the University of Virginia, Charlottesville, Virginia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah A.","family":"Tersey","sequence":"additional","affiliation":[{"name":"From the University of Virginia, Charlottesville, Virginia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Craig S.","family":"Nunemaker","sequence":"additional","affiliation":[{"name":"From the University of Virginia, Charlottesville, Virginia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jerry L.","family":"Nadler","sequence":"additional","affiliation":[{"name":"From the University of Virginia, Charlottesville, Virginia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1167","reference":[{"key":"2022031303285154700_R1","doi-asserted-by":"crossref","unstructured":"Atkinson MA, Leiter EH: The NOD mouse model of type 1 diabetes: as good as it gets?Nat Med\u20085:601\u2013604,1999","DOI":"10.1038\/9442"},{"key":"2022031303285154700_R2","doi-asserted-by":"crossref","unstructured":"Maier LM, Wicker LS: Genetic susceptibility to type 1 diabetes. 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