Bone Geometry and Strength Measurements in Aging Mice with the oim Mutation
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Mice with the naturally occurring oim mutation allows investigation of bone pathobiology in the setting of one mutation: a G deletion in the murine Cola-2 gene (exon 52) encoding the proα2(I) C-propeptide. As a result, normal sized mRNA is transcribed, but no secreted protein has been identified in oim/oim fibroblasts or osteoblasts. Here we report longitudinal changes in body mass, bone geometry, and bone structural properties of femurs tested in torsion from wild type (+/+) mice and mice homozygous (oim/oim) and heterozygous (+/oim) for the oim mutation. Femurs from mice 3 months, 6 months, 12 months, and >18 months of age were dissected and X-ray films were taken in anterioposterior and mediolateral views to estimate the geometric properties. The metaphyseal ends of femurs were potted in polymethylemethacrylate and mounted on a torsional test fixture designed to convert axial tensile deformation to a torsional load using an INSTRON model 4204 materials tester. Compared with +/+ samples, peak torque at failure was reduced in oim/oim mice. Also, the geometric distribution of midshaft bone for oim/oim mice in terms of cortical area and polar moment was significantly reduced. However, the impact of the mutation on bone distribution was relatively minor for +/oim mice. Consistent with a type III classification in human OI patients, the presence of two nonfunctional alleles in homozygous oim mice significantly reduced body mass compared with age-matched wild type mice. However, no statistical difference in body mass was detected between +/oim and +/+ mice. The absence of a gross phenotypic difference between +/oim and +/+ mice demonstrates a milder phenotype in +/oim mice.
- Bone Geometry and Strength Measurements in Aging Mice with the oim Mutation
Calcified Tissue International
Volume 62, Issue 2 , pp 172-176
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- Key words: Bone — Collagen — Homotrimer — osteogenesis imperfecta —oim.
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- 1. Bone Metabolism Research Laboratory, Division of Geriatric Medicine and Gerontology, The Johns Hopkins Medical Institutions, Baltimore, Maryland 21224, USA, USA
- 2. Division of Orthopaedic Surgery, UMDNJ-Robert Wood Johnson Medical School, New Brunswick, New Jersey, USA, USA