title: Osteoporosis induced in mice by overproduction of interleukin 4.
abstract: 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.
authors.affiliation: Department of Pediatrics, University of Washington, Seattle 98195.
authors.forename: D B
authors.initials: DB
authors.lastname: Lewis
authors.forename: H D
authors.initials: HD
authors.lastname: Liggitt
authors.forename: E L
authors.initials: EL
authors.lastname: Effmann
authors.forename: S T
authors.initials: ST
authors.lastname: Motley
authors.forename: S L
authors.initials: SL
authors.lastname: Teitelbaum
authors.forename: K J
authors.initials: KJ
authors.lastname: Jepsen
authors.forename: S A
authors.initials: SA
authors.lastname: Goldstein
authors.forename: J
authors.initials: J
authors.lastname: Bonadio
authors.forename: J
authors.initials: J
authors.lastname: Carpenter
authors.forename: R M
authors.initials: RM
authors.lastname: Perlmutter
mesh_terms: D000199:Actins / Q000096:biosynthesis; D000818:Animals; D001842:Bone and Bones / Q000000981:diagnostic imaging / Q000473:pathology*; D005260:Female; D015847:Interleukin-4 / Q000096:biosynthesis*; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009856:Oncogene Proteins, Viral / Q000235:genetics; D010024:Osteoporosis / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology*; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D011505:Protein-Tyrosine Kinases / Q000235:genetics; D014057:Tomography, X-Ray Computed; D014158:Transcription, Genetic
chemical_list: D000199:Actins; D009856:Oncogene Proteins, Viral; D015847:Interleukin-4; D011505:Protein-Tyrosine Kinases; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck)