title: Bone geometry and strength measurements in aging mice with the oim mutation.
abstract: 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 proalpha2(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.
authors.affiliation: Bone Metabolism Research Laboratory, Division of Geriatric Medicine and Gerontology, The Johns Hopkins Medical Institutions, Baltimore, Maryland 21224, USA.
authors.forename: D J
authors.initials: DJ
authors.lastname: McBride
authors.forename: J R
authors.initials: JR
authors.lastname: Shapiro
authors.forename: M G
authors.initials: MG
authors.lastname: Dunn
mesh_terms: D000375:Aging / Q000235:genetics* / Q000473:pathology*; D019412:Anatomy, Cross-Sectional; D000818:Animals; D001842:Bone and Bones / Q000473:pathology* / Q000503:physiopathology*; D005260:Female; D005269:Femur / Q000000981:diagnostic imaging / Q000503:physiopathology; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D009154:Mutation; D010013:Osteogenesis Imperfecta / Q000235:genetics* / Q000503:physiopathology; D011859:Radiography; D013718:Tensile Strength; D014102:Torsion Abnormality