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 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.
Lewis
D B
DB
Department of Pediatrics, University of Washington, Seattle 98195.
Liggitt
H D
HD
Effmann
E L
EL
Motley
S T
ST
Teitelbaum
S L
SL
Jepsen
K J
KJ
Goldstein
S A
SA
Bonadio
J
J
Carpenter
J
J
Perlmutter
R M
RM
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
D000199:Actins; D009856:Oncogene Proteins, Viral; D015847:Interleukin-4; D011505:Protein-Tyrosine Kinases; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck)