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The role of hepatic XBP1 in FXR null mice

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X-box binding protein 1 (XBP1) is a key component of the unfolded protein response that is activated in response to ER stress. Farnesoid X receptor (FXR) null (Fxr-/-) mice have elevated bile acid levels and progressive liver injury. Hepatic XBP1 pathway is activated in older Fxr-/- mice. This project is to investigate the role of liver XBP1 in Fxr-/- mice. We generated mice with FXR and liver-specific XBP1 double knockout (DKO, Fxr-/-Xbp1LKO) and Fxr-/-Xbp1fl/fl single knockout (SKO) mice. Liver RNA was extracted from chow-fed male 8-10 weeks old SKO and DKO mice.

X盒结合蛋白1(X-box binding protein 1,XBP1)是未折叠蛋白反应的关键组分,该反应可在内质网应激(ER stress)刺激下被激活。法尼醇X受体(Farnesoid X receptor, FXR)敲除(Fxr-/-)小鼠体内胆汁酸水平升高,并伴随进行性肝损伤。老年Fxr-/-小鼠的肝脏XBP1通路会被激活。本研究旨在探究肝脏XBP1在Fxr-/-小鼠中的作用。我们构建了FXR与肝脏特异性XBP1双敲除(DKO, Fxr-/-Xbp1LKO)小鼠,以及Fxr-/-Xbp1fl/fl单敲除(SKO)小鼠。我们从普通饲料喂养的8~10周龄雄性SKO与DKO小鼠体内提取了肝脏RNA。

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