{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T15:09:57Z","timestamp":1787065797956,"version":"build-2736575974"},"reference-count":47,"publisher":"The Company of Biologists","issue":"2","license":[{"start":{"date-parts":[[2020,9,4]],"date-time":"2020-09-04T00:00:00Z","timestamp":1599177600000},"content-version":"vor","delay-in-days":1677,"URL":"http:\/\/creativecommons.org\/licenses\/by\/3.0"}],"funder":[{"DOI":"10.13039\/501100001322","name":"Medical Research Council","doi-asserted-by":"publisher","award":["G0601268"],"award-info":[{"award-number":["G0601268"]}],"id":[{"id":"10.13039\/501100001322","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000291","name":"Kidney Research UK","doi-asserted-by":"publisher","award":["19\/2012"],"award-info":[{"award-number":["19\/2012"]}],"id":[{"id":"10.13039\/501100000291","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000690","name":"Research Councils UK","doi-asserted-by":"publisher","award":["EP\/E50036611"],"award-info":[{"award-number":["EP\/E50036611"]}],"id":[{"id":"10.13039\/501100000690","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["091840\/Z\/10\/Z"],"award-info":[{"award-number":["091840\/Z\/10\/Z"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2016,2,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Collagen IV is a major component of basement membranes, and mutations in COL4A1, which encodes collagen IV alpha chain 1, cause a multisystemic disease encompassing cerebrovascular, eye and kidney defects. However, COL4A1 renal disease remains poorly characterized and its pathomolecular mechanisms are unknown. We show that Col4a1 mutations in mice cause hypotension and renal disease, including proteinuria and defects in Bowman's capsule and the glomerular basement membrane, indicating a role for Col4a1 in glomerular filtration. Impaired sodium reabsorption in the loop of Henle and distal nephron despite elevated aldosterone levels indicates that tubular defects contribute to the hypotension, highlighting a novel role for the basement membrane in vascular homeostasis by modulation of the tubular response to aldosterone. Col4a1 mutations also cause diabetes insipidus, whereby the tubular defects lead to polyuria associated with medullary atrophy and a subsequent reduction in the ability to upregulate aquaporin\u00a02 and concentrate urine. Moreover, haematuria, haemorrhage and vascular basement membrane defects confirm an important vascular component. Interestingly, although structural and compositional basement membrane defects occurred in the glomerulus and Bowman's capsule, no tubular basement membrane defects were detected. By contrast, medullary atrophy was associated with chronic ER stress, providing evidence for cell-type-dependent molecular mechanisms of Col4a1 mutations. These data show that both basement membrane defects and ER stress contribute to Col4a1 renal disease, which has important implications for the development of treatment strategies for collagenopathies.<\/jats:p>","DOI":"10.1242\/dmm.021741","type":"journal-article","created":{"date-parts":[[2016,2,2]],"date-time":"2016-02-02T11:56:46Z","timestamp":1454414206000},"page":"165-176","source":"Crossref","is-referenced-by-count":52,"title":["ER stress and basement membrane defects combine to cause glomerular and tubular renal disease resulting from\n                    <i>Col4a1<\/i>\n                    mutations in mice"],"prefix":"10.1242","volume":"9","author":[{"given":"Frances E.","family":"Jones","sequence":"first","affiliation":[{"name":"Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, G12 8QQ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew A.","family":"Bailey","sequence":"additional","affiliation":[{"name":"British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, EH16 4TJ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lydia S.","family":"Murray","sequence":"additional","affiliation":[{"name":"Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, G12 8QQ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinhui","family":"Lu","sequence":"additional","affiliation":[{"name":"Wellcome Trust Centre for Cell-Matrix Research, Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"McNeilly","sequence":"additional","affiliation":[{"name":"Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, G12 8QQ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ursula","family":"Schl\u00f6tzer-Schrehardt","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University of Erlangen-N\u00fcrnberg, D-91054 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel","family":"Lennon","sequence":"additional","affiliation":[{"name":"Wellcome Trust Centre for Cell-Matrix Research, Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshikazu","family":"Sado","sequence":"additional","affiliation":[{"name":"Division of Immunology, Shigei Medical Research Institute, Okayama 701-02, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David G.","family":"Brownstein","sequence":"additional","affiliation":[{"name":"Division of Pathology, School of Molecular and Clinical Medicine, University of Edinburgh, Edinburgh, EH16 4TJ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John J.","family":"Mullins","sequence":"additional","affiliation":[{"name":"British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, EH16 4TJ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karl E.","family":"Kadler","sequence":"additional","affiliation":[{"name":"Wellcome Trust Centre for Cell-Matrix Research, Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom","family":"Van Agtmael","sequence":"additional","affiliation":[{"name":"Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, G12 8QQ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","reference":[{"key":"2021042513084935300_DMM021741C1","doi-asserted-by":"publisher","first-page":"1471","DOI":"10.1681\/ASN.2008101086","article-title":"Cellular origins of type IV collagen networks in developing glomeruli","volume":"20","author":"Abrahamson","year":"2009","journal-title":"J. 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