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    Please use this identifier to cite or link to this item: http://ir.cnu.edu.tw/handle/310902800/10438

    標題: 誘導性剔除成鼠雄性素受體基因對骨頭衡定性之影響
    Altered Bone Homeostasis in Adult Inducible Androgen Receptor Knockout mice
    作者: 王舒右
    Shu-yo Wang
    貢獻者: 莊一全
    關鍵字: 雄性素受體
    抗粘病毒基因1- 雄性素受體剔除鼠
    androgen receptor
    cre-lox system
    conditional knockout
    日期: 2008
    上傳時間: 2009-03-11 11:41:52 (UTC+8)
    摘要: 全面性雄性素受體剔除小鼠(ARKO mice)在生長期間跟野生型小鼠
    (Wild type mice)相比,其骨質密度(BMD)雖然減少了,但我們卻發現
    其骨頭的型態塑造(bone modeling)亦不正常。因為人類骨質疏鬆症
    的再塑期(bone remodeling)出了問題。因此這種全面性雄性素受體剔除之
    們製作一隻誘導性雄性素受體剔除鼠,策略是將購自Jackson Lab 誘導性的
    抗粘病毒基因 1-可力鼠(Mx1-cre)與我們的雄性素受體洛克斯鼠(flox-AR
    mice)交配產生抗粘病毒基因 1-雄性素受體剔除(Mx1-ARKO)。除非注
    射干擾素甲(interferon- ),否則這隻老鼠的雄性素受體將保持正常。我們
    示,分析Mx1-ARKO 小鼠各器官之雄性素受體基因的量,其肝臟、骨頭、
    腦的雄性素受體基因的量跟野生型小鼠相比都有減少(P < 0.05)。微斷層掃
    瞄(Micro CT)分析股骨、脊椎骨之骨小梁的各參數,其骨頭的質量確實
    也有減少(P < 0.05),皮質骨(Cortical bone)的厚度(Thickness)和週長
    (Perimeter)也都有差異(P < 0.05)。由於Mx1-ARKO 小鼠骨頭的質量都
    展有莫大的幫助。全面性雄性素受體剔除小鼠(ARKO mice)在生長期間跟?..
    During the mouse bone growth, the bone mineral density(BMD)of general
    androgen receptor knockout(ARKO)mice is lower than that of WT(wild type)
    mice. However, we found that the bone modeling in adult ARKO mice is
    abnormal. In human beings, the bone modeling in osteoporosis patients is
    normal, but the bone remodeling in osteoporosis patients is defective. Therefore,
    these general ARKO mice are not a suitable animal model for studying
    osteoporosis. In order to mimic the human osteoporosis model, we proposed to
    induce ARKO in adult mice. Our strategy was to cross-match our flox-AR mice
    with the inducible MX1-cre mice. AR would only be knocked out in
    MX1-ARKO mice after interferon-alpha injection. We then compared the
    difference in bone metabolism between ARKO and intact AR mice to investigate
    the role of AR in bone remodeling. We found that the AR RNA level in liver,
    bone, brain and testis in Mx1 ARKO mice was less than that in WT mice(P <
    0.05). The analysis of bone parameters in trabecular bone of femur and vertebral
    bone by Micro-CT revealed that the bone mass indeed decreased(P < 0.05).
    There also were differences in thickness and perimeter in cortical bone. Because
    of the decreased bone mass in Mx1-ARKO mice, the tolerance to external force
    was worse and bones are more fragile and easy-broken compared to WT mice.
    In conclusion, we created a knockout AR model in adult mice after normal
    bone development. And the results showed the inducible ARKO mice became
    osteoporotic after losing AR. The MX1-ARKO model in our study was proven
    to be a powerful tool to study the role of androgen receptor in bone homeostasis.
    The collecting knowledge will greatly influence the treatment and the new drug
    development for osteoporosis in the future by modulating the AR activity.
    關聯: 校內校外均不公開
    Appears in Collections:[生物科技系(所)] 博碩士論文

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