生物谷：来自欧洲分子生物实验室（EMBL）以及Michigan大学的科学家最近发现了一个防止多种肾脏疾病发生的基因。在最新一期在线版Nature Genetics上，研究小组报道这一基因的变异将导致人类和老鼠中发生NPHP肾病。
NPHP是一种在儿童时期肾脏衰退导致的疾病，它最终需要通过肾移植来治疗。而这一新发现或许能带来有效的、非侵入性的治疗手段。
肾脏帮助人类排出有害废物，影响这一过程的疾病非常严重，而且机制并不清楚。NPHP就是这样的疾病，它导致30岁之前肾脏就会衰竭，因此在年轻时就接受肾移植是唯一的治疗手段。而EMBL的Mathias Treier和他的小组利用新型老鼠模型找到了NPHP的分子机制，并有望带来全新治疗方法。
Mathias Treier说：“患有NPHP的老鼠模型肾收缩模式类似人类。在生命早期它们的肾脏细胞开始死亡，并表现出一切NPHP的症状。这是首次利用老鼠证明这一机制，发生变异的基因是GLIS2。”
GLIS2通常用来防止成年肾脏细胞死亡。它通过关闭启动细胞死亡程序的基因做到这一点。而GLIS2的变异会重新激发有害基因，从而导致大量肾脏细胞死亡。最终器官会收缩、改变结构从而影响肾脏正常功能。
为了寻找GLIS2对人类的影响，Michigan大学的Friedhelm Hildebrandt以及他的小组分析了NPHP病人的基因。结果小组发现，和老鼠模型一样的是，其中某些病人在GLIS2基因同样发生了变异，这一结果确认了GLIS2同样是导致人类NPHP病的一个关键因素。 （引自教育部科技发展中心）
原文链接：http://www.physorg.com/news103120629.html
原始出处:
Nature Genetics
Published online: 8 July 2007 | doi:10.1038/ng2072
Loss of GLIS2 causes nephronophthisis in humans and mice by increased apoptosis and fibrosis
Massimo Attanasio1,8, N Henriette Uhlenhaut2,8, Vitor H Sousa2,7, John F O'Toole1, Edgar Otto1, Katrin Anlag2, Claudia Klugmann2, Anna-Corina Treier2, Juliana Helou1, John A Sayer1, Dominik Seelow3,4, Gudrun Nürnberg3,4, Christian Becker3,4, Albert E Chudley5, Peter Nürnberg3,6, Friedhelm Hildebrandt1 & Mathias Treier2
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Nephronophthisis (NPHP), an autosomal recessive kidney disease, is the most frequent genetic cause of end-stage renal failure in the first three decades of life. Positional cloning of the six known NPHP genes1, 2, 3, 4 has linked its pathogenesis to primary cilia function3, 5. Here we identify mutation of GLIS2 as causing an NPHP-like phenotype in humans and mice, using positional cloning and mouse transgenics, respectively. Kidneys of Glis2 mutant mice show severe renal atrophy and fibrosis starting at 8 weeks of age. Differential gene expression studies on Glis2 mutant kidneys demonstrate that genes promoting epithelial-to-mesenchymal transition and fibrosis are upregulated in the absence of Glis2. Thus, we identify Glis2 as a transcription factor mutated in NPHP and demonstrate its essential role for the maintenance of renal tissue architecture through prevention of apoptosis and fibrosis.
Departments of Pediatrics and of Human Genetics, University of Michigan, Ann Arbor, Michigan 48109, USA.
Developmental Biology Unit, European Molecular Biology Laboratory, D-69117 Heidelberg, Germany.
Cologne Center for Genomics, University of Cologne, D-50674 Cologne, Germany.
RZPD Deutsches Ressourcenzentrum für Genomforschung GmbH, D-14059 Berlin, Germany.
Departments of Pediatrics and Child Health, Biochemistry and Medical Genetics, University of Manitoba, Winnipeg, Manitoba R3E3P4, Canada.
Institute for Genetics, University of Cologne, D-50674 Cologne, Germany.
Present address: Smilow Research Center, New York University, New York, New York 10016, USA.
These authors contributed equally to this work.
Correspondence to: Friedhelm Hildebrandt1 e-mail: fhilde@med.umich.edu
Correspondence to: Mathias Treier2 e-mail: treier@embl.de
