A faithful JAGGED1 haploinsufficiency mouse model of arteriohepatic dysplasia (Alagille syndrome) after all.
A faithful JAGGED1 haploinsufficiency mouse model of arteriohepatic dysplasia (Alagille syndrome) after all.
复制标题
毕竟是忠实的 JAGGED1 单倍体不足小鼠模型，是动脉肝发育不良（Alagille 综合征）的模型。
DOI：
10.1002/hep.28338
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发表时间：
2016
期刊：
影响因子：
--
通讯作者：
Huppert,StaceyS
中科院分区：
文献类型：
--
作者：
Huppert,StaceyS
The association of human JAGGED1 (JAG1) mutations in more than 94% of definitive Alagille syndrome (ALGS) cases reveals an involvement of the Notch pathway. 1 Studies in model organisms from invertebrates to vertebrates have established that Notch signaling is used reiteratively to provide communication between two cells, actively influencing cell fate decisions. Therefore, it is not surprising that ALGS is a pleiotropic disease, characterized by developmental abnormalities presenting in organs such as liver, heart, eye, kidney, and pancreas, as well as skeletal and craniofacial abnormalities. A common and distinguishing feature of this sporadic genetic disorder is cholestasis due to paucity of intrahepatic bile ducts (IHBDs). 2Mouse models investigating the loss or gain of Notch pathway components in specific hepatic cell lineages have elucidated the importance of Notch signal reception within the hepatoblast lineage for IHBD morphogenesis. The Notch ligand JAG1 is presented by portal vein (PV) mesenchyme to activate Notch receptors on juxtaposed bipotential hepatoblasts establishing IHBD architecture. 3 However, two very perplexing questions remain. First, given that ALGS is a dominantly inherited disease, why does the loss of one copy of Jag1 in mice not recapitulate ALGS IHBD paucity? 3 Reports analyzing the phenotype of the null Jag1dDSL allele, 4, 5 generated by targeted deletion of the C-terminal portion of the DELTA/SERRATE/LAG-2 (DSL) domain required for interaction with NOTCH receptors, have not
