{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T03:01:43Z","timestamp":1790737303362,"version":"4.1.0"},"reference-count":46,"publisher":"National Academy of Sciences","issue":"37","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2011,9,13]]},"abstract":"<jats:p>\n                    Pierson syndrome is a congenital nephrotic syndrome with ocular and neurological defects caused by mutations in\n                    <jats:italic>LAMB2<\/jats:italic>\n                    , the gene encoding the basement membrane protein laminin \u03b22 (Lam\u03b22). It is the kidney glomerular basement membrane (GBM) that is defective in Pierson syndrome, as Lam\u03b22 is a component of laminin-521 (LM-521; \u03b15\u03b22\u03b31), the major laminin in the mature GBM. In both Pierson syndrome and the\n                    <jats:italic>\n                      Lamb2\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    <\/jats:italic>\n                    mouse model for this disease, laminin \u03b21 (Lam\u03b21), a structurally similar homolog of Lam\u03b22, is marginally increased in the GBM, but it fails to fully compensate for the loss of Lam\u03b22, leading to the filtration barrier defects and nephrotic syndrome. Here we generated several lines of Lam\u03b21 transgenic mice and used them to show that podocyte-specific Lam\u03b21 expression in\n                    <jats:italic>Lamb2<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice abrogates the development of nephrotic syndrome, correlating with a greatly extended lifespan. In addition, the more Lam\u03b21 was expressed, the less urinary albumin was excreted. Transgenic Lam\u03b21 expression increased the level of Lam\u03b15 in the GBM of rescued mice, consistent with the desired increased deposition of laminin-511 (\u03b15\u03b21\u03b31) 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\n                    <jats:italic>LAMB1<\/jats:italic>\n                    in podocytes, should it become achievable, would likely lessen the severity of nephrotic syndrome in patients carrying\n                    <jats:italic>LAMB2<\/jats:italic>\n                    mutations.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1108269108","type":"journal-article","created":{"date-parts":[[2011,8,29]],"date-time":"2011-08-29T22:04:21Z","timestamp":1314655461000},"page":"15348-15353","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":53,"title":["Forced expression of laminin \u03b21 in podocytes prevents nephrotic syndrome in mice lacking laminin \u03b22, a model for Pierson syndrome"],"prefix":"10.1073","volume":"108","author":[{"given":"Jung Hee","family":"Suh","sequence":"first","affiliation":[{"name":"Renal Division, Department of Internal Medicine and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George","family":"Jarad","sequence":"additional","affiliation":[{"name":"Renal Division, Department of Internal Medicine and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rene G.","family":"VanDeVoorde","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Hypertension, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey H.","family":"Miner","sequence":"additional","affiliation":[{"name":"Renal Division, Department of Internal Medicine and"},{"name":"Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, MO 63110; and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2011,8,29]]},"reference":[{"key":"e_1_3_3_1_2","first-page":"184","article-title":"An unusual congenital and familial congenital malformative combination involving the eye and kidney","volume":"12","author":"Pierson M","year":"1963","unstructured":"M Pierson, J Cordier, F Hervouuet, G Rauber, An unusual congenital and familial congenital malformative combination involving the eye and kidney. 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