OSTEOPOROSIS INDUCED IN MICE BY OVERPRODUCTION OF INTERLEUKIN-4

Osteoporosis is a common disease in which loss of bone mass results in skeletal fragility. The development of therapies for this disorder ha s been hampered by the lack of a convenient animal model. Here we desc ribe a disorder in bone homeostasis in transgenic mice that inappropri ately express the cytokine interleukin 4 (IL-4) under the direction of the lymphocyte-specific proximal promoter for the lck gene. Bone dise ase in lck-IL-4 mice appeared to result from markedly decreased bone f ormation 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 sev ere osteoporosis of both cortical and trabecular bone. Osteoporosis wa s observed in two independently derived founder animals, indicating th at this phenotype was directly mediated by the IL-4 transgene.