Osteoporosis induced in mice by overproduction of interleukin 4.

作者：David B. Lewis, H. Denny Liggitt, E L Effmann, S. Timothy Motley, Steven L. Teitelbaum, Karl J. Jepsen, Steven A. Goldstein, Jacob D. Bonadio, Jeffery H. Carpenter, Roger M. Perlmutter · 发表于：Proceedings of the National Academy of Sciences · 年份：1993 · DOI：10.1073/pnas.90.24.11618 · 被引用次数：167 · 研究领域：Bone Metabolism and Diseases、Cytokine Signaling Pathways and Interactions、Bone and Dental Protein Studies

Osteoporosis is a common disease in which loss of bone mass results in skeletal fragility. The development of therapies for this disorder has been hampered by the lack of a convenient animal model. Here we describe a disorder in bone homeostasis in transgenic mice that inappropriately express the cytokine interleukin 4 (IL-4) under the direction of the lymphocyte-specific proximal promoter for the lck gene. Bone disease in lck-IL-4 mice appeared to result from markedly decreased bone formation by osteoblasts, features strikingly similar to those observed in cases of severe low-turnover human involutional osteoporosis. By 2 months of age, female and male lck-IL-4 mice invariably developed severe osteoporosis of both cortical and trabecular bone. Osteoporosis was observed in two independently derived founder animals, indicating that this phenotype was directly mediated by the IL-4 transgene.