生物谷：來自歐洲分子生物實(shí)驗(yàn)室（EMBL）以及Michigan大學(xué)的科學(xué)家最近發(fā)現(xiàn)了一個(gè)防止多種腎臟疾病發(fā)生的基因,。在最新一期在線版Nature Genetics上，研究小組報(bào)道這一基因的變異將導(dǎo)致人類和老鼠中發(fā)生NPHP腎病,。
NPHP是一種在兒童時(shí)期腎臟衰退導(dǎo)致的疾病，它最終需要通過腎移植來治療,。而這一新發(fā)現(xiàn)或許能帶來有效的,、非侵入性的治療手段。
腎臟幫助人類排出有害廢物,，影響這一過程的疾病非常嚴(yán)重,，而且機(jī)制并不清楚。NPHP就是這樣的疾病,，它導(dǎo)致30歲之前腎臟就會衰竭,，因此在年輕時(shí)就接受腎移植是唯一的治療手段。而EMBL的Mathias Treier和他的小組利用新型老鼠模型找到了NPHP的分子機(jī)制,，并有望帶來全新治療方法,。
Mathias Treier說：“患有NPHP的老鼠模型腎收縮模式類似人類。在生命早期它們的腎臟細(xì)胞開始死亡,，并表現(xiàn)出一切NPHP的癥狀,。這是首次利用老鼠證明這一機(jī)制，發(fā)生變異的基因是GLIS2,。”
GLIS2通常用來防止成年腎臟細(xì)胞死亡,。它通過關(guān)閉啟動細(xì)胞死亡程序的基因做到這一點(diǎn)。而GLIS2的變異會重新激發(fā)有害基因,，從而導(dǎo)致大量腎臟細(xì)胞死亡,。最終器官會收縮、改變結(jié)構(gòu)從而影響腎臟正常功能,。
為了尋找GLIS2對人類的影響,，Michigan大學(xué)的Friedhelm Hildebrandt以及他的小組分析了NPHP病人的基因。結(jié)果小組發(fā)現(xiàn),，和老鼠模型一樣的是,，其中某些病人在GLIS2基因同樣發(fā)生了變異，這一結(jié)果確認(rèn)了GLIS2同樣是導(dǎo)致人類NPHP病的一個(gè)關(guān)鍵因素,。 （引自教育部科技發(fā)展中心）
原文鏈接：http://www.physorg.com/news103120629.html
原始出處:
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: [email protected]
Correspondence to: Mathias Treier2 e-mail: [email protected]
