Transgenic overexpression of prothymosin α induces development of polycystic kidney disease

Kuo Jung Li, Ai Li Shiau, Yuan Yow Chiou, Yi Te Yo, Chao Liang Wu

研究成果: Article同行評審

17 引文 斯高帕斯(Scopus)


Background. Polycystic kidney disease (PKD) is a genetic disorder characterized by development of renal cysts and progressive renal dysfunction. Renal tissues from both PKD patients and rodent models of PKD show elevated c-myc expression. Prothymosin α (ProT) is positively regulated by c-myc through binding to the E box of its promoter. Through creating transgenic mice and clinical studies, we sought to investigate whether ProT overexpression contributes to PKD development. Methods. ProT heterozygous and homozygous transgenic mice were generated and characterized. Morphologic, histologic, immunohistochemical, and biochemical analyses of the transgenic mice were performed. Results. Two transgenic lines that represented integration at two different loci of the chromosomes were generated. ProT overexpression in the kidneys of homozygous transgenic mice induced a PKD phenotype, which included polycystic kidneys, elevated blood urea nitrogen (BUN), and lethality at about 10 days of age. Similar overexpression pattern of ProT was noted in cystic kidneys of the transgenic mice as well as in human autosomal-recessive PKD (ARPKD) and autosomal-dominant PKD (ADPKD) kidneys. ProT protein levels in the kidneys and urine as well as renal mRNA level of epithelial growth factor receptor (EGFR) of homozygous ProT transgenic mice were significantly higher than heterozygous or nontransgenic littermates. Furthermore, the heterozygous transgenic mice at 17 months of age also developed mild cystic kidneys. Conclusion. Transgenic mice overexpressing ProT represent a novel model for PKD and may provide insights into PKD development. ProT, like c-myc and EGFR, may contribute to the development of renal cysts and may be a potential noninvasive diagnostic molecule of PKD.

頁(從 - 到)1710-1722
期刊Kidney international
出版狀態Published - 2005 5月

All Science Journal Classification (ASJC) codes

  • 腎臟病學


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