Phenotypic characterization of a novel HO-1 depletion model in the rat

详细信息    查看全文

• 作者：Vassilios Atsaves ; Maria G. Detsika ; Elpida Poulaki…
• 关键词：Kidney ; Heme oxygenase ; 1 (HO ; 1) ; Rat model
• 刊名：Transgenic Research
• 出版年：2017
• 出版时间：February 2017
• 年：2017
• 卷：26
• 期：1
• 页码：51-64
• 全文大小：
• 刊物类别：Biomedical and Life Sciences
• 刊物主题：Animal Genetics and Genomics; Plant Genetics & Genomics; Transgenics; Biomedical Engineering/Biotechnology; Genetic Engineering; Molecular Medicine;
• 出版者：Springer International Publishing
• ISSN：1573-9368
• 卷排序：26

文摘

Although the protective role of HO-1 induction in various forms of kidney disease is well established, mechanisms other than heme catabolism to biliverdin, bilirubin and carbon monoxide have recently been identified. Unraveling these mechanisms requires the generation of appropriate animal models. The present study describes the generation of a HO-1 deficient Hmox1−/− rat model and characterizes its renal and extrarenal phenotype. Hmox1−/− rats had growth retardation and splenomegaly compared to their Hmox1+/+ littermates. Focal segmental glomerulosclerosis-type lesions and interstitial inflammatory infiltrates were prominent morphologic findings and were associated with increased blood urea nitrogen, serum creatinine and albuminuria. There was no increase in iron deposition in glomeruli, tubules or interstitium. Iron deposition in spleen and liver was reduced. Electron microscopic examination of glomeruli revealed edematous podocytes with scant areas of foot process effacement but otherwise well preserved processes and slit-diaphragms. Of the filtration barrier proteins examined, β-catenin expression was markedly reduced both in glomeruli and extrarenal tissues. Since the rat is the preferred laboratory animal in experimental physiology and pathophysiology, the rat model of HO-1 deficiency may provide a novel tool for investigation of the role of this enzyme in renal function and disease.