Bone geometry and strength measurements in aging mice with the oim mutation
Bone geometry and strength measurements in aging mice with the oim mutation
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DOI：
10.1007/s002239900412
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发表时间：
1998-02-01
影响因子：
4.2
通讯作者：
Dunn, MG
中科院分区：
文献类型：
--
作者：
McBride, DJ;Shapiro, JR;Dunn, MG
具有自然发生的oim突变的小鼠可以在一种突变的情况下研究骨病理生物学：编码pro alpha 2（I）C-前肽的小鼠Cola-2基因（外显子52）中的G缺失。结果，正常大小的mRNA被转录，但在oim/oim成纤维细胞或成骨细胞中没有发现分泌的蛋白质。在这里，我们报告了在扭转中测试的野生型（+/+）小鼠和oim突变纯合子（oim/oim）和杂合子（+/oim）小鼠股骨的体重、骨几何形状和骨结构特性的纵向变化。解剖来自3月龄、6月龄、12月龄和> 18月龄小鼠的股骨，并在前后位和中侧位拍摄X线片以估计几何特性。将股骨干骺端灌封在聚甲基丙烯酸甲酯中，并安装在扭转试验夹具上，该夹具设计用于使用INSTRON 4204型材料试验机将轴向拉伸变形转换为扭转载荷。与+/+样品相比，oim/oim小鼠的峰值失效扭矩降低。此外，在皮质面积和极矩方面，oim/oim小鼠中轴骨的几何分布显著降低。然而，对于+/oim小鼠，突变对骨分布的影响相对较小。与III型分类在人类OI患者一致，两个非功能性等位基因的纯合子oim小鼠的存在显着降低体重与年龄匹配的野生型小鼠相比。然而，在+/oim和+/+小鼠之间没有检测到体重的统计学差异。+/oim和+/+小鼠之间不存在总体表型差异，表明+/oim小鼠的表型较温和。
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 pro alpha 2(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.