{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:33:34Z","timestamp":1792787614026,"version":"4.5.0"},"reference-count":0,"publisher":"American Society for Clinical Investigation","license":[{"start":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T00:00:00Z","timestamp":1790208000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIDDK","award":["5R01DK126804"],"award-info":[{"award-number":["5R01DK126804"]}],"id":[{"id":"https:\/\/ror.org\/00adh9b73","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"\n ADAMTS9<\/jats:italic>\n mutations cause the ciliopathies nephronophthisis and Joubert syndrome. Here we demonstrated that deletion of ADAMTS9 in the proximal nephron led to polycystic kidney development in mice. In males,\n Adamts9<\/jats:italic>\n deletion caused kidneys to become highly cystic while remaining small without undergoing enlargement. In contrast, female mice developed cystic kidneys at a slower rate. ADAMTS9 deletion disrupted ciliogenesis through the loss of cleavage of the ciliary transition zone (TZ) protein TMEM67, which led to loss of the MKS\/B9 module \u2013 a key component of the ciliary gate. Functional analysis of all eight ciliopathy patient variants of\n ADAMTS9<\/jats:italic>\n identified to date showed TMEM67 C-terminus failed to localize to the TZ, thus disrupting a key regulatory mechanism in patient renal ciliogenesis. Modeling ADAMTS9-mediated TMEM67 cleavage utilizing TMEM67-cleavage deficient mice revealed loss of TZ formation, but not elevated canonical Wnt signaling as the underlying mechanism driving cystogenesis.\n Adamts9<\/jats:italic>\n deletion led to comparatively intense interstitial collagen deposition, which likely restricted kidney enlargement and resulted in the characteristically small kidney phenotype seen in nephronophthisis. By comparative analysis of four interconnected polycystic kidney models, in addition to\n Pkd1<\/jats:italic>\n and\n Pkd2<\/jats:italic>\n deleted kidneys, we identified differential collagen homeostasis as a principle factor determining cystic kidney size and type.\n <\/jats:p>","DOI":"10.1172\/jci.insight.203950","type":"journal-article","created":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T16:00:41Z","timestamp":1790265641000},"source":"Crossref","is-referenced-by-count":0,"title":["Loss of ADAMTS9 disrupts ciliogenesis and collagen homeostasis resulting in Nephronophthisis-like polycystic kidneys"],"prefix":"10.1172","author":[{"given":"Sydney","family":"Fischer","sequence":"first","affiliation":[{"name":"Department of Pediatrics, University of Massachusetts Chan Medical School, Worcester, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karyn L.","family":"Robert","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Massachusetts Chan Medical School, Worcester, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manu","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Massachusetts Chan Medical School, Worcester, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Griffin I.","family":"Kane","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, University of Massachusetts Amherst, Amherst, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew A.","family":"Kavanaugh","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Physiology and the Jared Grantham Kidney Ins, University of Kansas Medical Center, Kansas City, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Physiology and the Jared Grantham Kidney Ins, University of Kansas Medical Center, Kansas City, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4619-4376","authenticated-orcid":true,"given":"Pamela V.","family":"Tran","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Physiology and the Jared Grantham Kidney Ins, University of Kansas Medical Center, Kansas City, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prabhani U.","family":"Atukorale","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, University of Massachusetts Amherst, Amherst, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sumeda","family":"Nandadasa","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Massachusetts Chan Medical School, Worcester, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2026,9,24]]},"container-title":["JCI Insight"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/insight.jci.org\/articles\/view\/203950\/files\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T16:00:42Z","timestamp":1790265642000},"score":1,"resource":{"primary":{"URL":"http:\/\/insight.jci.org\/articles\/view\/203950"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,24]]},"references-count":0,"alternative-id":["10.1172\/jci.insight.203950"],"URL":"https:\/\/doi.org\/10.1172\/jci.insight.203950","relation":{},"ISSN":["2379-3708"],"issn-type":[{"value":"2379-3708","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,24]]}}}