{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T16:35:30Z","timestamp":1793205330872,"version":"4.5.0"},"reference-count":20,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"10","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JASN"],"published-print":{"date-parts":[[2016,10]]},"abstract":"\n CKD is a significant health concern with an underlying genetic component. Multiple genome\u2013wide association studies (GWASs) strongly associated CKD with the shroom family member 3 (\n SHROOM3<\/jats:italic>\n ) gene, which encodes an actin-associated protein important in epithelial morphogenesis. However, the role of\n SHROOM3<\/jats:italic>\n in kidney development and function is virtually unknown. Studies in zebrafish and rat showed that alterations in\n Shroom3<\/jats:italic>\n can result in glomerular dysfunction. Furthermore, human\n SHROOM3<\/jats:italic>\n variants can induce impaired kidney function in animal models. Here, we examined the temporal and spatial expression of Shroom3 in the mammalian kidney. We detected Shroom3 expression in the condensing mesenchyme, Bowman\u2019s capsule, and developing and mature podocytes in mice.\n Shroom3<\/jats:italic>\n null (\n Shroom3Gt\/Gt<\/jats:italic>\n ) mice showed marked glomerular abnormalities, including cystic and collapsing\/degenerating glomeruli, and marked disruptions in podocyte arrangement and morphology. These podocyte-specific abnormalities are associated with altered Rho\u2013kinase\/myosin II signaling and loss of apically distributed actin. Additionally,\n Shroom3<\/jats:italic>\n heterozygous (\n Shroom3Gt\/+<\/jats:italic>\n ) mice showed developmental irregularities that manifested as adult-onset glomerulosclerosis and proteinuria. Taken together, our results establish the significance of Shroom3 in mammalian kidney development and progression of kidney disease. Specifically, Shroom3 maintains normal podocyte architecture in mice\n via<\/jats:italic>\n modulation of the actomyosin network, which is essential for podocyte function. Furthermore, our findings strongly support the GWASs that suggest a role for SHROOM3 in human kidney disease.\n <\/jats:p>","DOI":"10.1681\/asn.2015060621","type":"journal-article","created":{"date-parts":[[2016,9,30]],"date-time":"2016-09-30T13:23:40Z","timestamp":1475241820000},"page":"2965-2973","source":"Crossref","is-referenced-by-count":66,"title":["Developmental Origins for Kidney Disease Due to Shroom3 Deficiency"],"prefix":"10.1681","volume":"27","author":[{"given":"Hadiseh","family":"Khalili","sequence":"first","affiliation":[{"name":"Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Sull","sequence":"additional","affiliation":[{"name":"Physiology and Pharmacology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanjay","family":"Sarin","sequence":"additional","affiliation":[{"name":"Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felix J.","family":"Boivin","sequence":"additional","affiliation":[{"name":"Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rami","family":"Halabi","sequence":"additional","affiliation":[{"name":"Physiology and Pharmacology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno","family":"Svajger","sequence":"additional","affiliation":[{"name":"Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aihua","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valerie Wenche","family":"Cui","sequence":"additional","affiliation":[{"name":"Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Drysdale","sequence":"additional","affiliation":[{"name":"Physiology and Pharmacology and"},{"name":"Pediatrics, University of Western Ontario, London, Ontario, Canada; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darren","family":"Bridgewater","sequence":"additional","affiliation":[{"name":"Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada;"},{"name":"Hamilton Center for Kidney Research, St. Josephs Healthcare, Hamilton, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2016,3,3]]},"reference":[{"key":"B1-20231016","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1016\/j.cmet.2010.05.009","article-title":"Chronic kidney disease and GWAS: \u201cThe proper study of mankind is man.\u201d","volume":"11","author":"Price","year":"2010","journal-title":"Cell Metab"},{"key":"B2-20231016","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1097\/CCM.0000000000000039","article-title":"Timing of continuous renal replacement therapy and mortality in critically ill children*.","volume":"42","author":"Modem","year":"2014","journal-title":"Crit Care Med"},{"key":"B3-20231016","doi-asserted-by":"crossref","first-page":"2183","DOI":"10.1056\/NEJMoa1310345","article-title":"APOL1 risk variants, race, and progression of chronic kidney disease.","volume":"369","author":"Parsa","year":"2013","journal-title":"N Engl J Med"},{"key":"B4-20231016","doi-asserted-by":"crossref","first-page":"1844","DOI":"10.1016\/S0140-6736(14)60659-0","article-title":"Rare inherited kidney diseases: Challenges, opportunities, and perspectives.","volume":"383","author":"Devuyst","year":"2014","journal-title":"Lancet"},{"key":"B5-20231016","doi-asserted-by":"crossref","first-page":"712","DOI":"10.1038\/ng.377","article-title":"Multiple loci associated with indices of renal function and chronic kidney disease.","volume":"41","author":"K\u00f6ttgen","year":"2009","journal-title":"Nat Genet"},{"key":"B6-20231016","doi-asserted-by":"crossref","first-page":"e1002292","DOI":"10.1371\/journal.pgen.1002292","article-title":"Association of eGFR-related loci identified by GWAS with incident CKD and ESRD.","volume":"7","author":"B\u00f6ger","year":"2011","journal-title":"PLoS Genet"},{"key":"B7-20231016","doi-asserted-by":"crossref","first-page":"e1001045","DOI":"10.1371\/journal.pgen.1001045","article-title":"Genome-wide association studies of serum magnesium, potassium, and sodium concentrations identify six loci influencing serum magnesium levels.","volume":"6","author":"Meyer","year":"2010","journal-title":"PLoS Genet"},{"key":"B8-20231016","doi-asserted-by":"crossref","first-page":"2125","DOI":"10.1016\/j.cub.2003.11.054","article-title":"Shroom induces apical constriction and is required for hingepoint formation during neural tube closure.","volume":"13","author":"Haigo","year":"2003","journal-title":"Curr Biol"},{"key":"B9-20231016","doi-asserted-by":"crossref","first-page":"1431","DOI":"10.1242\/dev.02828","article-title":"Shroom family proteins regulate gamma-tubulin distribution and microtubule architecture during epithelial cell shape change.","volume":"134","author":"Lee","year":"2007","journal-title":"Development"},{"key":"B10-20231016","doi-asserted-by":"crossref","first-page":"5177","DOI":"10.1242\/dev.067868","article-title":"A Trio-RhoA-Shroom3 pathway is required for apical constriction and epithelial invagination.","volume":"138","author":"Plageman","year":"2011","journal-title":"Development"},{"key":"B11-20231016","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1016\/S0092-8674(00)81537-8","article-title":"Shroom, a PDZ domain-containing actin-binding protein, is required for neural tube morphogenesis in mice.","volume":"99","author":"Hildebrand","year":"1999","journal-title":"Cell"},{"key":"B12-20231016","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1172\/JCI76902","article-title":"Intronic locus determines SHROOM3 expression and potentiates renal allograft fibrosis.","volume":"125","author":"Menon","year":"2015","journal-title":"J Clin Invest"},{"key":"B13-20231016","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1101\/gr.182881.114","article-title":"Shroom3 contributes to the maintenance of the glomerular filtration barrier integrity.","volume":"25","author":"Yeo","year":"2015","journal-title":"Genome Res"},{"key":"B14-20231016","doi-asserted-by":"crossref","first-page":"1493","DOI":"10.1242\/dev.019646","article-title":"Shroom3-mediated recruitment of Rho kinases to the apical cell junctions regulates epithelial and neuroepithelial planar remodeling.","volume":"135","author":"Nishimura","year":"2008","journal-title":"Development"},{"key":"B15-20231016","doi-asserted-by":"crossref","first-page":"2159","DOI":"10.1681\/ASN.2008030312","article-title":"Podocyte-selective deletion of dicer induces proteinuria and glomerulosclerosis.","volume":"19","author":"Shi","year":"2008","journal-title":"J Am Soc Nephrol"},{"key":"B16-20231016","doi-asserted-by":"crossref","first-page":"1395","DOI":"10.1016\/j.ajpath.2014.01.018","article-title":"\u03b2-Catenin overexpression in the metanephric mesenchyme leads to renal dysplasia genesis via cell-autonomous and non-cell-autonomous mechanisms.","volume":"184","author":"Sarin","year":"2014","journal-title":"Am J Pathol"},{"key":"B17-20231016","doi-asserted-by":"crossref","first-page":"718","DOI":"10.1681\/ASN.2010050562","article-title":"\u03b2-catenin causes renal dysplasia via upregulation of Tgf\u03b22 and Dkk1.","volume":"22","author":"Bridgewater","year":"2011","journal-title":"J Am Soc Nephrol"},{"key":"B18-20231016","doi-asserted-by":"crossref","first-page":"1369","DOI":"10.1681\/ASN.V1271369","article-title":"Chemokine expression precedes inflammatory cell infiltration and chemokine receptor and cytokine expression during the initiation of murine lupus nephritis.","volume":"12","author":"P\u00e9rez de Lema","year":"2001","journal-title":"J Am Soc Nephrol"},{"key":"B19-20231016","doi-asserted-by":"crossref","first-page":"1035","DOI":"10.1038\/ncb2828","article-title":"Stromal-epithelial crosstalk regulates kidney progenitor cell differentiation.","volume":"15","author":"Das","year":"2013","journal-title":"Nat Cell Biol"},{"key":"B20-20231016","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1681\/ASN.2013050452","article-title":"Unraveling the role of podocyte turnover in glomerular aging and injury.","volume":"25","author":"Wanner","year":"2014","journal-title":"J Am Soc Nephrol"}],"container-title":["Journal of the American Society of Nephrology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ovid.com\/00001751-201610000-00010","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T19:28:20Z","timestamp":1786130900000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ovid.com\/00001751-201610000-00010"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,3,3]]},"references-count":20,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2016]]}},"URL":"https:\/\/doi.org\/10.1681\/asn.2015060621","relation":{},"ISSN":["1046-6673","1533-3450"],"issn-type":[{"value":"1046-6673","type":"print"},{"value":"1533-3450","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,3,3]]}}}