Characterization of the renal phenotype in a mouse model of Marfan syndrome
Characterization of the renal phenotype in a mouse model of Marfan syndrome
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DOI：
10.1007/s00428-004-1081-6
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发表时间：
2004-10-01
期刊：
影响因子：
3.5
通讯作者：
Amann, K
中科院分区：
文献类型：
--
作者：
Hartner, A;Eifert, T;Amann, K
微纤维蛋白原纤蛋白-1在肾脏的血管系统和肾小球中大量表达。马凡氏综合征的病因是马凡氏综合征。这种疾病最常见的并发症是由于血管壁的弹性不足而导致的主动脉扩张。一些病例报告描述了马凡氏综合征患者的肾小球疾病，并且已证实了肾发生中涉及到β-淀粉样蛋白-1。为了研究Rheumin-1在肾脏发育和功能中的作用，我们描述了Rheumin-1低表达小鼠的肾脏表型。通过形态计量学和体视学方法评价肾脏组织学。相对肾脏重量、每日尿排泄量、尿白蛋白排泄量、血清和尿肌酐以及血清尿素与野生型小鼠无差异。肾小球数目和肾毛细血管化正常。肾滤过表面的大小在野生型小鼠和白细胞介素-1低表达小鼠中相当。无肾小球、肾血管或肾小管间质损伤迹象。但肾小球体积和系膜面积减少。肾小球细胞数量没有变化，但肾小球系膜细胞的细胞体积显着降低，在肾小球中的repein-1表达不足的小鼠。因此，尽管在野生型动物的肾小球中高丰度的β-淀粉样蛋白-1，β-淀粉样蛋白-1的低表达并不导致肾小球的功能缺陷。肾组织学改变仅为轻微，肾小球体积和系膜面积减少，可能是由于系膜细胞体积减少所致。
The microfibrillar protein fibrillin-1 is expressed abundantly in the vasculature and the glomerulus of the kidney. Mutations in the fibrillin-1 gene lead to Marfan syndrome. The most common complication of this disease is aortic dilatation due to elastic deficiencies of the vascular wall. Several case reports describe glomerular disease in patients with Marfan syndrome, and fibrillin-1 has been implicated in nephrogenesis. To study the role of fibrillin-1 in renal development and function, we characterized the renal phenotype of fibrillin-1-underexpressing mice. Kidney histology was evaluated by means of morphometry and stereology. Relative kidney weights, daily urine excretion, urinary albumin excretion, serum and urinary creatinine, as well as serum urea were not different than wild-type mice. Glomerular number and renal capillarization were normal. The size of the renal filtration surface was comparable in wild-type and fibrillin-1-underexpressing mice. There was no indication for glomerular, renal vascular, or tubulointerstitial injury. However, glomerular volume and mesangial area were reduced. No changes in glomerular cell numbers were detected, but the cellular volume of mesangial cells was significantly lower in glomeruli of fibrillin-1-underexpressing mice. Thus, despite the high abundance of fibrillin-1 in glomeruli of wild-type animals, underexpression of fibrillin-1 did not lead to functional deficiencies of the glomerulus. Alterations in renal histology were only subtle with a reduced glomerular volume and mesangial area likely due to a reduced mesangial cell volume.