| First Author | Suh JH | Year | 2011 |
| Journal | Proc Natl Acad Sci U S A | Volume | 108 |
| Issue | 37 | Pages | 15348-53 |
| PubMed ID | 21876163 | Mgi Jnum | J:176446 |
| Mgi Id | MGI:5291863 | Doi | 10.1073/pnas.1108269108 |
| Citation | Suh JH, et al. (2011) Forced expression of laminin {beta}1 in podocytes prevents nephrotic syndrome in mice lacking laminin {beta}2, a model for Pierson syndrome. Proc Natl Acad Sci U S A 108(37):15348-53 |
| abstractText | 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 beta2 (Lambeta2). It is the kidney glomerular basement membrane (GBM) that is defective in Pierson syndrome, as Lambeta2 is a component of laminin-521 (LM-521; alpha5beta2gamma1), the major laminin in the mature GBM. In both Pierson syndrome and the Lamb2(-/-) mouse model for this disease, laminin beta1 (Lambeta1), a structurally similar homolog of Lambeta2, is marginally increased in the GBM, but it fails to fully compensate for the loss of Lambeta2, leading to the filtration barrier defects and nephrotic syndrome. Here we generated several lines of Lambeta1 transgenic mice and used them to show that podocyte-specific Lambeta1 expression in Lamb2(-/-) mice abrogates the development of nephrotic syndrome, correlating with a greatly extended lifespan. In addition, the more Lambeta1 was expressed, the less urinary albumin was excreted. Transgenic Lambeta1 expression increased the level of Lamalpha5 in the GBM of rescued mice, consistent with the desired increased deposition of laminin-511 (alpha5beta1gamma1) trimers. Ultrastructural analysis revealed occasional knob-like subepithelial GBM thickening but intact podocyte foot processes in aged rescued 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. |
