Molecular analysis on osteoporosis using transgenic mice

使用转基因小鼠进行骨质疏松症的分子分析

• 批准号: 08044258
• 负责人: NODA Masaki
• 金额: $ 6.02万
• 依托单位: Tokyo Medical and Dental University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for international Scientific Research
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08044258/
• 关键词: osteoporosis; osteoblast; osteoclast; carvaria; ascorbic acid; knock out animal; tartrate resistant acid phosphatase; osteopontin; トランスジェニック動物; 骨形成; 骨吸収; 石灰化; 酒石酸耐性賛成フォスファターゼ; ノックアウト; スクリーニング

Murine osteopontin gene knock out mice were produced and the phenotypes were analyzed. Major axons were included in the region which was replaced with an insertion cassette sequence. ES cells obtained by the homologous recombination were introduced into blastocysts. Mice were born and were mated to generate knock out mice. Tibiae and femora were taken out of the knock out mice and were analyzed for their morphology. Similar features have been found in control and knock out mice in most of the gross skeletal architecture and histology. However, in vitro osteoclastogenesis monitored by examining tartrate resistant acid phosphatase was found to be different. Also calvarial osteoblastic cells were also shown to be normal to form bone in the presence of ascorbic acid. These mice show the importance of osteopontin in bone metabolism.

制备鼠骨桥蛋白基因敲除小鼠并分析其表型。主要轴突包含在被插入盒序列替换的区域中。将通过同源重组获得的ES细胞导入囊胚中。小鼠出生并交配以产生基因敲除小鼠。从基因敲除小鼠中取出胫骨和股骨并分析其形态。在对照和敲除小鼠的大部分总体骨骼结构和组织学中也发现了类似的特征。然而，通过检查酒石酸抗性酸性磷酸酶监测的体外破骨细胞生成却发现不同。此外，颅骨成骨细胞在抗坏血酸存在下也显示出正常形成骨的能力。这些小鼠显示了骨桥蛋白在骨代谢中的重要性。

项目成果

Toshiyuki Kawa-uchi: "Messenger RNA Expression of the Genes Encoding Receptors for Bone Morphogenetic Protein (BMP) and Transforming Growth Factor-β (TGF-β) in the Cells from the Posterior Longitudinal Ligament in Cervical Spine" Endocrine. 5・3. 307-314 (

Toshiyuki Kawa-uchi：“颈椎后纵韧带细胞中骨形态发生蛋白 (BMP) 和转化生长因子-β (TGF-β) 受体基因的信使 RNA 表达”内分泌 5・3。 307-314（

Y.Liu、M.Noda et al.: "Scleraxis is expressed in C2C12 myoblasts and its level is down-regulated by bone morphogenetic protein-2 (BMP2)." Journal of Cellular Biochemistry. 67. 1-9 (1997)

Y. Liu, M. Noda 等人：“Scleraxis 在 C2C12 成肌细胞中表达，其水平受骨形态发生蛋白 2 (BMP2) 下调。” Journal of Cellular Biochemistry 67. 1-9 (1997)。

Y.Liu、M.Noda et al: "Sclerotome-related helix-loop-helix type transcription factor (scleraxis) mRNA is expressed in osteoblasts and its level is enhanced by type-β transforming growth factor" Journal of Endocrinology. 151. 491-499 (1996)

Y. Liu, M. Noda 等人：“巩膜相关螺旋-环-螺旋型转录因子 (scleraxis) mRNA 在成骨细胞中表达，β 型转化生长因子可增强其水平”《内分泌学杂志》151. 491。 -499 (1996)

Y. Liu, M. Noda et al.: "Soleraxis is expressed in C2C12 myoblasts and its level is down-regulated by bone morphoger, etic protein-2 (BMP2)." Journal of Cellular Biochemistry. 67. 1-9 (1997)

Y. Liu、M. Noda 等人：“Soleraxis 在 C2C12 成肌细胞中表达，其水平受到骨形态生成器 etic Protein-2 (BMP2) 的下调。”

T.Yamashita, A.Nifuji, K.Furuya, Y.Nabeshima and M.Noda: "Elongation of the epiphyseal trabecular bone associated with precocious aging in transgenic mice carrying an insertional mutation in Klotho gene locus." Journal of Bone and Mineral Research. (in pr

T.Yamashita、A.Nifuji、K.Furuya、Y.Nabeshima 和 M.Noda：“在 Klotho 基因座中携带插入突变的转基因小鼠中，骨骺骨小梁的延长与性早熟相关。”