{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T02:56:29Z","timestamp":1787021789702,"version":"build-2736575974"},"update-to":[{"DOI":"10.1371\/journal.pgen.1009603","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2021,6,30]],"date-time":"2021-06-30T00:00:00Z","timestamp":1625011200000}}],"reference-count":108,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2021,6,18]],"date-time":"2021-06-18T00:00:00Z","timestamp":1623974400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003130","name":"Research Foundation Flanders","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100003130","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Ghent University","award":["01N04516C"],"award-info":[{"award-number":["01N04516C"]}]},{"name":"Ghent University","award":["BOFMET2015000401"],"award-info":[{"award-number":["BOFMET2015000401"]}]},{"name":"Fund for Scientific Research","award":["G035620N"],"award-info":[{"award-number":["G035620N"]}]},{"DOI":"10.13039\/100010665","name":"H2020 Marie Sk\u0142odowska-Curie Actions","doi-asserted-by":"publisher","award":["794365"],"award-info":[{"award-number":["794365"]}],"id":[{"id":"10.13039\/100010665","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosgenetics.org"],"crossmark-restriction":false},"short-container-title":["PLoS Genet"],"abstract":"<jats:p>\n                    The inability to maintain a strictly regulated endo(lyso)somal acidic pH through the proton-pumping action of the vacuolar-ATPases (v-ATPases) has been associated with various human diseases including heritable connective tissue disorders. Autosomal recessive (AR) cutis laxa (CL) type 2C syndrome is associated with genetic defects in the\n                    <jats:italic>ATP6V1E1<\/jats:italic>\n                    gene and is characterized by skin wrinkles or loose redundant skin folds with pleiotropic systemic manifestations. The underlying pathological mechanisms leading to the clinical presentations remain largely unknown. Here, we show that loss of\n                    <jats:italic>atp6v1e1b<\/jats:italic>\n                    in zebrafish leads to early mortality, associated with craniofacial dysmorphisms, vascular anomalies, cardiac dysfunction, N-glycosylation defects, hypotonia, and epidermal structural defects. These features are reminiscent of the phenotypic manifestations in ARCL type 2C patients. Our data demonstrates that loss of\n                    <jats:italic>atp6v1e1b<\/jats:italic>\n                    alters endo(lyso)somal protein levels, and interferes with non-canonical v-ATPase pathways\n                    <jats:italic>in vivo<\/jats:italic>\n                    . In order to gain further insights into the processes affected by loss of\n                    <jats:italic>atp6v1e1b<\/jats:italic>\n                    , we performed an untargeted analysis of the transcriptome, metabolome, and lipidome in early\n                    <jats:italic>atp6v1e1b<\/jats:italic>\n                    -deficient larvae. We report multiple affected pathways including but not limited to oxidative phosphorylation, sphingolipid, fatty acid, and energy metabolism together with profound defects on mitochondrial respiration. Taken together, our results identify complex pathobiological effects due to loss of\n                    <jats:italic>atp6v1e1b in vivo<\/jats:italic>\n                    .\n                  <\/jats:p>","DOI":"10.1371\/journal.pgen.1009603","type":"journal-article","created":{"date-parts":[[2021,6,18]],"date-time":"2021-06-18T13:37:34Z","timestamp":1624023454000},"page":"e1009603","update-policy":"https:\/\/doi.org\/10.1371\/journal.pgen.corrections_policy","source":"Crossref","is-referenced-by-count":11,"title":["Loss of zebrafish atp6v1e1b, encoding a subunit of vacuolar ATPase, recapitulates human ARCL type 2C syndrome and identifies multiple pathobiological signatures"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5102-975X","authenticated-orcid":true,"given":"Lore","family":"Pottie","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wouter","family":"Van Gool","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7350-9009","authenticated-orcid":true,"given":"Michiel","family":"Vanhooydonck","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franz-Georg","family":"Hanisch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0337-2999","authenticated-orcid":true,"given":"Geert","family":"Goeminne","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1062-0564","authenticated-orcid":true,"given":"Andreja","family":"Rajkovic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Coucke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9241-5980","authenticated-orcid":true,"given":"Patrick","family":"Sips","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9743-4205","authenticated-orcid":true,"given":"Bert","family":"Callewaert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2021,6,18]]},"reference":[{"key":"pgen.1009603.ref001","first-page":"183341","article-title":"Regulation and function of V-ATPases in physiology and disease. 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