Dept. of Cell and Developmental Biology, SUNY Upstate Medical Univ., 750 E. Adams St., Syracuse, NY 13210, USA.
Am J Physiol Renal Physiol. 2012 Oct;303(7):F1099-106. doi: 10.1152/ajprenal.00251.2012. Epub 2012 Jul 18.
Myosin 1e (myo1e) is an actin-dependent molecular motor that plays an important role in kidney functions. Complete knockout of myo1e in mice and Myo1E mutations in humans are associated with nephrotic syndrome and focal segmental glomerulosclerosis. In this paper, we tested the hypothesis that myo1e is necessary for normal functions of glomerular visceral epithelial cells (podocytes) using podocyte-targeted knockout of myo1e. Myo1e was selectively knocked out in podocytes using Cre-mediated recombination controlled by the podocin promoter. Myo1e loss from podocytes resulted in proteinuria, podocyte foot process effacement, and glomerular basement membrane disorganization. Our findings indicate that myo1e expression in podocytes is necessary for normal glomerular filtration and that podocyte defects are likely to represent the primary pathway leading to glomerular disease associated with Myo1E mutations.
肌球蛋白 1e（myo1e）是一种依赖肌动蛋白的分子马达，在肾脏功能中发挥着重要作用。小鼠中 myo1e 的完全敲除和人类 Myo1E 突变与肾病综合征和局灶节段性肾小球硬化有关。在本文中，我们使用足细胞靶向敲除 myo1e 来检验肌球蛋白 1e 对于肾小球内脏上皮细胞（足细胞）正常功能是必需的这一假设。使用由 podocin 启动子控制的 Cre 介导的重组来选择性地在足细胞中敲除 myo1e。足细胞中肌球蛋白 1e 的缺失导致蛋白尿、足细胞足突消失和肾小球基底膜紊乱。我们的研究结果表明，足细胞中肌球蛋白 1e 的表达对于正常肾小球滤过是必需的，并且足细胞缺陷可能代表导致与 Myo1E 突变相关的肾小球疾病的主要途径。
