Inducible inactivation of Notch1 causes nodular regenerative hyperplasia in mice
Inducible inactivation of Notch1 causes nodular regenerative hyperplasia in mice
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DOI：
10.1002/hep.20571
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发表时间：
2005-03-01
期刊：
影响因子：
13.5
通讯作者：
Heim, MH
中科院分区：
文献类型：
--
作者：
Croquelois, A;Blindenbacher, A;Heim, MH
人类Jagged1基因(JAG1)是Alagille综合征的基因，这一发现表明Notch信号在胆管内稳态中起着重要作用。这一信号通路的功能研究一直很困难，因为Jagged1、Notch1或Notch2靶向突变的小鼠具有胚胎致死表型。我们以前使用干扰素诱导的Cre重组酶转基因结合loxP侧翼的Notch1基因产生了可诱导的Notch1中断的小鼠。我们使用这种有条件的Notch1基因敲除小鼠模型来研究Notch1信号在肝细胞增殖和分化中的作用。Notch1的缺失并没有导致胆管稀少，但令人惊讶的是，它导致了肝细胞的持续增殖。总而言之，在Notch1失活后的几周内，小鼠出现了结节状再生性增生，肝脏没有血管变化。
The discovery that the human Jagged1 gene (JAG1) is the Alagille syndrome disease gene indicated that Notch signaling has an important role in bile duct homeostasis. The functional study of this signaling pathway has been difficult because mice with targeted mutations in Jagged1, Notch1, or Notch2 have an embryonic lethal phenotype. We have previously generated mice with inducible Notch1 disruption using an interferon-inducible Cre-recombinase transgene in combination with the loxP flanked Notch1 gene. We used this conditional Notch1 knockout mouse model to investigate the role of Notch1 signaling in liver cell proliferation and differentiation. Deletion of Notch1 did not result in bile duct paucity, but, surprisingly, resulted in a continuous proliferation of hepatocytes. In conclusion, within weeks after Notch1 inactivation, the mice developed nodular regenerative hyperplasia without vascular changes in the liver.