IR@PKUHSC  > 北京大学第一临床医学院
学科主题临床医学
Novel UMOD mutations in familial juvenile hyperuricemic nephropathy lead to abnormal uromodulin intracellular trafficking
Liu, Maojing1; Chen, Yuqing1; Liang, Yu1; Liu, Ying1; Wang, Suxia1,2; Hou, Ping1; Zhang, Hong1; Zhao, Minghui1
关键词Umod Familial Juvenile Hyperuricemic Nephropathy Uromodulin Tamm-horsfall Protein Fjhn
刊名GENE
2013-12-01
DOI10.1016/j.gene.2013.08.041
531期:2页:363-369
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Genetics & Heredity
研究领域[WOS]Genetics & Heredity
关键词[WOS]TAMM-HORSFALL GLYCOPROTEIN ; UNFOLDED PROTEIN RESPONSE ; ENDOPLASMIC-RETICULUM ; GENE ; IDENTIFICATION ; EXPRESSION ; SECRETION ; DISEASE ; BIOLOGY ; CLUSTER
英文摘要

Background: Familial juvenile hyperuricemic nephropathy (FJHN) is an autosomal dominant disorder characterized by hyperuricemia and progressive chronic kidney disease. Uromodulin gene (UMOD) mutations, leading to abnormalities of uromodulin intracellular trafficking contribute to the progress of the disease.

Methods: We did UMOD screening in three Chinese FJHN families. We thus constructed mutant uromodulin express plasmids by site-mutagenesis from wild type uromodulin vector and transfected them into HEK293 (human embryonic kidney) cells. And then we detected uromodulin expression by western blot and observed intracellular distribution by immunofluorescence.

Results: We found three heterozygous mutations. Mutation Val109Glu (c.326T/A; p.Val109Glu) and mutation Pro236Gln (c.707C/A; p.Pro236GIn) were newly indentified mutations in two distinct families (family F1 and family F3). Another previously reported UMOD mutation Cys248Trp (c744C/G; p.Cys248Trp) was detected in family F2. Phenotypes varied both within the same family and between different families. Uromodulin expression is abnormal in the patient biopsy. Functional analysis of mutation showed that mutant types of uromodulin were secreted into the supernatant medium much less when compared with wild type. In mutant type uromodulin transfected cells, intracellular uromodulin localized less in the Golgi apparatus and more in endoplasmic reticulum(ER).

Conclusions: Our results suggested that the novel uromodulin mutations found in the Chinese families lead to misfolded protein, which was retained in the endoplasmic reticulum, finally contributed to the phenotype of FJHN. (C) 2013 Elsevier B.V. All rights reserved.

语种英语
WOS记录号WOS:000326846800030
Citation statistics
Cited Times:7[WOS]   [WOS Record]     [Related Records in WOS]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/51048
Collection北京大学第一临床医学院
北京大学第一临床医学院_电镜室
北京大学第一临床医学院_肾脏内科
作者单位1.Peking Univ, Key Lab Chron Kidney Dis Prevent & Treatment, Key Lab Renal Dis,Hosp 1,Minist Educ, Renal Div,Dept Med,Inst Nephrol,Minist Hlth China, Beijing 100871, Peoples R China
2.Peking Univ, Lab Electron Microscopy, Hosp 1, Beijing 100034, Peoples R China
Recommended Citation
GB/T 7714
Liu, Maojing,Chen, Yuqing,Liang, Yu,et al. Novel UMOD mutations in familial juvenile hyperuricemic nephropathy lead to abnormal uromodulin intracellular trafficking[J]. GENE,2013,531(2):363-369.
APA Liu, Maojing.,Chen, Yuqing.,Liang, Yu.,Liu, Ying.,Wang, Suxia.,...&Zhao, Minghui.(2013).Novel UMOD mutations in familial juvenile hyperuricemic nephropathy lead to abnormal uromodulin intracellular trafficking.GENE,531(2),363-369.
MLA Liu, Maojing,et al."Novel UMOD mutations in familial juvenile hyperuricemic nephropathy lead to abnormal uromodulin intracellular trafficking".GENE 531.2(2013):363-369.
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