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In particular, these genetic variants have illuminated the roles of the podocyte, glomerular basement membrane and endothelial cell in glomerular filtration. However, in a significant number of familial and early onset cases, an underlying mutation cannot be identified, indicating that there are likely to be multiple unknown genes with roles in glomerular permeability. We now show how the combination of <jats:italic>N<\/jats:italic>\u2010ethyl\u2010<jats:italic>N<\/jats:italic>\u2010nitrosourea mutagenesis and next\u2010generation sequencing could be used to identify the range of mutations affecting these pathways. Using this approach, we isolated a novel mouse strain with a viable nephrotic phenotype and used whole\u2010genome sequencing to isolate a causative hypomorphic mutation in <jats:italic>Lamb2<\/jats:italic>. This discovery generated a model for one part of the spectrum of human Pierson's syndrome and provides a powerful proof of principle for accelerating gene discovery and improving our understanding of inherited forms of renal disease. Copyright \u00a9 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley &amp; Sons, Ltd<\/jats:bold><\/jats:p>","DOI":"10.1002\/path.4308","type":"journal-article","created":{"date-parts":[[2013,11,29]],"date-time":"2013-11-29T12:02:41Z","timestamp":1385726561000},"page":"18-26","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Next\u2010generation sequencing to dissect hereditary nephrotic syndrome in mice identifies a hypomorphic mutation in <i>Lamb2<\/i> and models Pierson's syndrome"],"prefix":"10.1002","volume":"233","author":[{"given":"Katherine R","family":"Bull","sequence":"first","affiliation":[{"name":"Nuffield Department of Medicine and Wellcome Trust Centre for Human Genetics Oxford University UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Mason","sequence":"additional","affiliation":[{"name":"Nuffield Department of Medicine and Wellcome Trust Centre for Human Genetics Oxford University 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