A Novel N-ethyl-N-nitrosourea-Induced Mutation in Phospholipase C gamma 2 
Causes Inflammatory Arthritis, Metabolic Defects, and Male Infertility In Vitro 
in a Murine Model

Abe, K.; Fuchs, H.; Boersma, A.; Hans, W.; Yu, P.; Kalaydjiev, S.; Klaften, M.; Adler, T.; Calzada-Wack, J.; Mossbrugger, I.; Rathkolb, B.; Rozman, J.; Prehn, C.; Maraslioglu, M.; Kametani, Y.; Shimada, S.; Adamski, J.; Busch, D. H.; Esposito, I.; Klingenspor, M.; Wolf, E.; Wurst, W.; Gailus-Durner, V.; Katan, M.; Marschall, S.; Soewarto, D.; Wagner, S.; de Angelis, M. H.

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A Novel N-ethyl-N-nitrosourea-Induced Mutation in Phospholipase C gamma 2 Causes Inflammatory Arthritis, Metabolic Defects, and Male Infertility In Vitro in a Murine Model

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Wurst, W.
Max Planck Institute of Psychiatry, Max Planck Society;

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Citation

Abe, K., Fuchs, H., Boersma, A., Hans, W., Yu, P., Kalaydjiev, S., et al. (2011). A Novel N-ethyl-N-nitrosourea-Induced Mutation in Phospholipase C gamma 2 Causes Inflammatory Arthritis, Metabolic Defects, and Male Infertility In Vitro in a Murine Model. Arthritis and Rheumatism, 63(5), 1301-1311.

Cite as: https://hdl.handle.net/11858/00-001M-0000-000E-8EAE-E

Abstract

Objective. 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. Methods. In a large-scale N-ethyl-N-nitrosourea mutagenesis project, the Ali14 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 Ali14/+ mice was performed in the German Mouse Clinic. Results. A novel missense mutation in the phospholipase C gamma 2 gene (Plcg2) was identified in Ali14/+ mice. Because of the hyperreactive external entry of calcium observed in cultured B cells and other in vitro experiments, the Ali14 mutation is thought to be a novel gain-of-function allele of Plcg2. Findings from systematic screening of Ali14/+ mice demonstrated various phenotypic changes: an abnormally high T cell: B cell