{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,4]],"date-time":"2026-04-04T12:41:39Z","timestamp":1775306499178,"version":"3.50.1"},"reference-count":44,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2011,4,27]],"date-time":"2011-04-27T00:00:00Z","timestamp":1303862400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatism"],"published-print":{"date-parts":[[2011,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>It is difficult to identify a single causative factor for inflammatory arthritis because of the multifactorial nature of the disease. This study was undertaken to dissect the molecular complexity of systemic inflammatory disease, utilizing a combined approach of mutagenesis and systematic phenotype screening in a murine model.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In a large\u2010scale <jats:italic>N<\/jats:italic>\u2010ethyl\u2010<jats:italic>N<\/jats:italic>\u2010nitrosourea mutagenesis project, the <jats:italic>Ali14<\/jats:italic> mutant mouse strain was established because of dominant inheritance of spontaneous swelling and inflammation of the hind paws. Genetic mapping and subsequent candidate gene sequencing were conducted to find the causative gene, and systematic phenotyping of <jats:italic>Ali14<\/jats:italic>\/+ mice was performed in the German Mouse Clinic.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A novel missense mutation in the <jats:italic>phospholipase C\u03b32<\/jats:italic> gene (<jats:italic>Plcg2<\/jats:italic>) was identified in <jats:italic>Ali14<\/jats:italic>\/+ mice. Because of the hyperreactive external entry of calcium observed in cultured B cells and other in vitro experiments, the <jats:italic>Ali14<\/jats:italic> mutation is thought to be a novel gain\u2010of\u2010function allele of <jats:italic>Plcg2<\/jats:italic>. Findings from systematic screening of <jats:italic>Ali14<\/jats:italic>\/+ mice demonstrated various phenotypic changes: an abnormally high T cell:B cell ratio, up\u2010regulation of Ig, alterations in body composition, and a reduction in cholesterol and triglyceride levels in peripheral blood. In addition, spermatozoa from <jats:italic>Ali14<\/jats:italic>\/+ mice failed to fertilize eggs in vitro, despite the normal fertility of the <jats:italic>Ali14<\/jats:italic>\/+ male mice in vivo.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These results suggest that the <jats:italic>Plcg2<\/jats:italic>\u2010mediated pathways play a crucial role in various metabolic and sperm functions, in addition to initiating and maintaining the immune system. These findings may indicate the importance of the <jats:italic>Ali14<\/jats:italic>\/+ mouse strain as a model for systemic inflammatory diseases and inflammation\u2010related metabolic changes in humans.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.30280","type":"journal-article","created":{"date-parts":[[2011,2,5]],"date-time":"2011-02-05T09:03:59Z","timestamp":1296896639000},"page":"1301-1311","source":"Crossref","is-referenced-by-count":48,"title":["A novel <i>N<\/i>\u2010ethyl\u2010<i>N<\/i>\u2010nitrosourea\u2013induced mutation in <i>phospholipase C\u03b32<\/i> causes inflammatory arthritis, metabolic defects, and male infertility in vitro in a murine 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