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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Forced expression of laminin 01 in podocytes prevents nephrotic syndrome in mice lacking laminin 02, a model for Pierson syndrome
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Forced expression of laminin 01 in podocytes prevents nephrotic syndrome in mice lacking laminin 02, a model for Pierson syndrome

机译：足细胞中层粘连蛋白01的强制表达可预防缺乏层粘连蛋白02（Pierson综合征的模型）的小鼠的肾病综合征

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Pierson syndrome is a congenital nephrotic syndrome with ocular and neurological defects caused by mutations in LAMB2, the gene encoding the basement membrane protein laminin (52 (Lamftt). It is the kidney glomerular basement membrane (GBM) that is defective in Pierson syndrome, as Lamp2 is a component of laminin-521 (LM-521; a5p2y1), the major laminin in the mature GBM. In both Pierson syndrome and the Lamb2~'~ mouse model for this disease, laminin (31 (Lamp"l), a structurally similar homolog of Lamp"2, is marginally increased in the GBM, but it fails to fully compensate for the loss of Lamp*2, leading to the filtration barrier defects and nephrotic syndrome. Here we generated several lines of Lam(51 transgenic mice and used them to show that podocyte-specific LampM expression in Lamb2~'~ mice abrogates the development of nephrotic syndrome, correlating with a greatly extended life-span. In addition, the more Lamj31 was expressed, the less urinary albumin was excreted. Transgenic Lampi expression increased the level of Lamoc5 in the GBM of rescued mice, consistent with the desired increased deposition of laminin-511 (ce5p"ly1) trimers. Ul-trastructural analysis revealed occasional knob-like subepithelial GBM thickening but intact podocyte foot processes in aged rest cued mice. These results suggest the possibility that up-regulation of LAMB1 in podocytes, should it become achievable, would likely lessen the severity of nephrotic syndrome in patients carrying LAMB2 mutations.
机译：皮尔森氏综合症是一种先天性肾病综合症，由于编码基底膜蛋白层粘连蛋白（52（Lamftt）的基因）LAMB2的突变而引起眼和神经功能缺损。皮尔森氏综合症的缺陷是肾小球基底膜（GBM）。 Lamp2是成熟的GBM中主要的层粘连蛋白laminin-521（LM-521; a5p2y1）的组成部分。在Pierson综合征和Lamb2'~~小鼠模型中，层粘连蛋白（31（Lamp“ 1）结构上相似的Lamp“ 2同源物在GBM中略有增加，但不能完全补偿Lamp * 2的损失，从而导致滤过屏障缺陷和肾病综合征。在这里，我们产生了多株Lam（51）转基因小鼠并用它们显示了Lamb2〜'〜小鼠中足细胞特异性LampM的表达消除了肾病综合征的发生，并与寿命大大延长有关；此外，Lamj31表达越多，尿白蛋白的排泄就越少。灯I表达增加了获救小鼠的GBM中Lamoc5的水平，这与层粘连蛋白511（ce5p“ ly1”）三聚体的所需增加的沉积相一致。 Ul-结构分析显示，老年提示小鼠中偶有旋钮样上皮下GBM增厚，但足细胞足突完整。这些结果表明，如果可能的话，足细胞中LAMB1的上调可能会减轻携带LAMB2突变的患者肾病综合征的严重性。

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