Alagille syndrome: Genetics and Functional Models.

Q1 Medicine

Current Pathobiology Reports Pub Date : 2017-09-01 DOI:10.1007/s40139-017-0144-8

Melissa A Gilbert, Nancy B Spinner

{"title":"Alagille syndrome: Genetics and Functional Models.","authors":"Melissa A Gilbert, Nancy B Spinner","doi":"10.1007/s40139-017-0144-8","DOIUrl":null,"url":null,"abstract":"Purpose of review: We review the genetics of the autosomal dominant, multi-system disorder, Alagille syndrome and provide a summary on how current functional models and emerging biotechnologies are equipped to guide scientists towards novel therapies. The importance of haploinsufficiency as a disease mechanism will be underscored throughout this discussion.Recent findings: Alagille syndrome, a human disorder affecting the liver, heart, vasculature, kidney, and other systems, is caused by mutations in the Notch signaling pathway ligand, Jagged1 (JAG1) or the receptor, NOTCH2. Current advances in animal modeling, in vitro cell culture, and human induced pluripotent stem cells, provide new opportunities in which to study disease mechanisms and manifestations.Summary: We anticipate that the availability of innovative functional models will allow scientists to test new gene therapies or small molecule treatments in physiologically-relevant systems. With these advances, we look forward to the development of new methods to help Alagille syndrome patients.","PeriodicalId":37014,"journal":{"name":"Current Pathobiology Reports","volume":"5 3","pages":"233-241"},"PeriodicalIF":0.0000,"publicationDate":"2017-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s40139-017-0144-8","citationCount":"25","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Current Pathobiology Reports","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1007/s40139-017-0144-8","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"Medicine","Score":null,"Total":0}

引用次数: 25

Abstract

Purpose of review: We review the genetics of the autosomal dominant, multi-system disorder, Alagille syndrome and provide a summary on how current functional models and emerging biotechnologies are equipped to guide scientists towards novel therapies. The importance of haploinsufficiency as a disease mechanism will be underscored throughout this discussion.

Recent findings: Alagille syndrome, a human disorder affecting the liver, heart, vasculature, kidney, and other systems, is caused by mutations in the Notch signaling pathway ligand, Jagged1 (JAG1) or the receptor, NOTCH2. Current advances in animal modeling, in vitro cell culture, and human induced pluripotent stem cells, provide new opportunities in which to study disease mechanisms and manifestations.

Summary: We anticipate that the availability of innovative functional models will allow scientists to test new gene therapies or small molecule treatments in physiologically-relevant systems. With these advances, we look forward to the development of new methods to help Alagille syndrome patients.

Abstract Image

查看原文本刊更多论文

阿拉吉尔综合征:遗传学和功能模型。

综述目的:我们回顾了常染色体显性遗传病、多系统疾病、Alagille综合征的遗传学，并概述了当前的功能模型和新兴的生物技术如何指导科学家开发新的治疗方法。单倍体功能不全作为一种疾病机制的重要性将在整个讨论中得到强调。最近发现:Alagille综合征是一种影响肝脏、心脏、脉管系统、肾脏和其他系统的人类疾病，由Notch信号通路配体Jagged1 (JAG1)或受体NOTCH2的突变引起。目前在动物模型、体外细胞培养和人诱导多能干细胞方面的进展，为研究疾病机制和表现提供了新的机会。总结:我们预计，创新功能模型的可用性将使科学家能够在生理相关系统中测试新的基因疗法或小分子疗法。有了这些进展，我们期待开发新的方法来帮助Alagille综合征患者。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Current Pathobiology Reports Medicine-Pathology and Forensic Medicine

CiteScore

6.40

自引率

0.00%

发文量

期刊介绍： This journal aims to offer expert review articles on the most important recent research pertaining to biological mechanisms underlying disease, including etiology, pathogenesis, and the clinical manifestations of cellular alteration. By providing clear, insightful, balanced contributions, the journal intends to serve those for whom the elucidation of new techniques and technologies related to pathobiology is essential. We accomplish this aim by appointing international authorities to serve as Section Editors in key subject areas across the field. Section Editors select topics for which leading experts contribute comprehensive review articles that emphasize new developments and recently published papers of major importance, highlighted by annotated reference lists. An Editorial Board of more than 20 internationally diverse members reviews the annual table of contents, ensures that topics include emerging research, and suggests topics of special importance to their country/region. Topics covered may include autophagy, cancer stem cells, induced pluripotential stem cells (iPS cells), inflammation and cancer, matrix pathobiology, miRNA in pathobiology, mitochondrial dysfunction/diseases, and myofibroblast.