{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T16:14:23Z","timestamp":1790957663761,"version":"4.1.0"},"reference-count":32,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2019,12,5]],"date-time":"2019-12-05T00:00:00Z","timestamp":1575504000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Peroxidasin (PXDN) is a unique peroxidase containing extracellular matrix motifs and stabilizes collagen IV networks by forming sulfilimine crosslinks. PXDN gene knockout in Caenorhabditis elegans (C. elegans) and Drosophila results in the demise at the embryonic and larval stages. PXDN mutations lead to severe eye disorders, including microphthalmia, cataract, glaucoma, and anterior segment dysgenesis in humans and mice. To investigate how PXDN loss of function affects organ development, we generated Pxdn knockout mice by deletion of exon 1 and its 5\u2032 upstream sequences of the Pxdn gene using the CRISPR\/Cas9 system. Loss of both PXDN expression and collagen IV sulfilimine cross-links was detected only in the homozygous mice, which showed completely or almost closed eyelids with small eyes, having no apparent external morphological defects in other organs. In histological analysis of eye tissues, the homozygous mice had extreme defects in eye development, including no eyeballs or drastically disorganized eye structures, whereas the heterozygous mice showed normal eye structure. Visual function tests also revealed no obvious functional abnormalities in the eyes between heterozygous mice and wild-type mice. Thus, these results suggest that PXDN activity is essential in eye development, and also indicate that a single allele of Pxdn gene is sufficient for eye-structure formation and normal visual function.<\/jats:p>","DOI":"10.3390\/ijms20246144","type":"journal-article","created":{"date-parts":[[2019,12,5]],"date-time":"2019-12-05T11:16:31Z","timestamp":1575544591000},"page":"6144","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Biallelic Deletion of Pxdn in Mice Leads to Anophthalmia and Severe Eye Malformation"],"prefix":"10.3390","volume":"20","author":[{"given":"Hyun-Kyung","family":"Kim","sequence":"first","affiliation":[{"name":"Cancer Research Institute, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea"},{"name":"Department of Medical Life Sciences, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyung A","family":"Ham","sequence":"additional","affiliation":[{"name":"Cancer Research Institute, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea"},{"name":"Department of Medical Life Sciences, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea"},{"name":"Department of Biomedicine &amp; Health Sciences, The Catholic University of Korea, Seoul 06591, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seung-Woo","family":"Lee","sequence":"additional","affiliation":[{"name":"Cancer Research Institute, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea"},{"name":"Department of Medical Life Sciences, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong Seok","family":"Choi","sequence":"additional","affiliation":[{"name":"Cancer Research Institute, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea"},{"name":"Department of Medical Life Sciences, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea"},{"name":"Department of Biomedicine &amp; Health Sciences, The Catholic University of Korea, Seoul 06591, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong-Sug","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Genetic Engineering Mouse, Macrogen Inc, Seoul 08511, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong Kyung","family":"Kim","sequence":"additional","affiliation":[{"name":"Korea Mouse Sensory Phenotyping Center (KMSPC), Yonsei University College of Medicine, Seoul 03722, Korea"},{"name":"Institute for Vision Research, Department of Ophthalmology, Yonsei University College of Medicine, Seoul 03722, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hae-Sol","family":"Shin","sequence":"additional","affiliation":[{"name":"Korea Mouse Sensory Phenotyping Center (KMSPC), Yonsei University College of Medicine, Seoul 03722, Korea"},{"name":"Institute for Vision Research, Department of Ophthalmology, Yonsei University College of Medicine, Seoul 03722, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyoung Yul","family":"Seo","sequence":"additional","affiliation":[{"name":"Korea Mouse Sensory Phenotyping Center (KMSPC), Yonsei University College of Medicine, Seoul 03722, Korea"},{"name":"Institute for Vision Research, Department of Ophthalmology, Yonsei University College of Medicine, Seoul 03722, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yejin","family":"Cho","sequence":"additional","affiliation":[{"name":"Severance Biomedical Science Institute, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul 03722, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5292-1280","authenticated-orcid":false,"given":"Ki Taek","family":"Nam","sequence":"additional","affiliation":[{"name":"Severance Biomedical Science Institute, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul 03722, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"In-Beom","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Anatomy, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young Ae","family":"Joe","sequence":"additional","affiliation":[{"name":"Cancer Research Institute, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea"},{"name":"Department of Medical Life Sciences, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea"},{"name":"Department of Biomedicine &amp; Health Sciences, The Catholic University of Korea, Seoul 06591, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,12,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1277","DOI":"10.2174\/138161209787846766","article-title":"Developmental and pathogenic mechanisms of basement membrane assembly","volume":"15","author":"Yurchenco","year":"2009","journal-title":"Curr. Pharm. Des."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1619","DOI":"10.1242\/dev.01037","article-title":"Collagen IV is essential for basement membrane stability but dispensable for initiation of its assembly during early development","volume":"131","author":"Poschl","year":"2004","journal-title":"Development"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1230","DOI":"10.1126\/science.1176811","article-title":"A sulfilimine bond identified in collagen IV","volume":"325","author":"Vanacore","year":"2009","journal-title":"Science"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"3161","DOI":"10.1093\/hmg\/ddi348","article-title":"Dominant mutations of Col4a1 result in basement membrane defects which lead to anterior segment dysgenesis and glomerulopathy","volume":"14","author":"McKie","year":"2005","journal-title":"Hum. Mol. Genet."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1002\/ana.21191","article-title":"COL4A1 mutation in Axenfeld-Rieger anomaly with leukoencephalopathy and stroke","volume":"62","author":"Sibon","year":"2007","journal-title":"Ann. Neurol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"946","DOI":"10.1016\/j.ajo.2012.11.028","article-title":"Variants of anterior segment dysgenesis and cerebral involvement in a large family with a novel COL4A1 mutation","volume":"155","author":"Rodahl","year":"2013","journal-title":"Am. J. Ophthalmol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1489","DOI":"10.1056\/NEJMoa053727","article-title":"Role of COL4A1 in small-vessel disease and hemorrhagic stroke","volume":"354","author":"Gould","year":"2006","journal-title":"N Engl. J. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.ajhg.2011.11.016","article-title":"De novo and inherited mutations in COL4A2, encoding the type IV collagen alpha2 chain cause porencephaly","volume":"90","author":"Yoneda","year":"2012","journal-title":"Am. J. Hum. Genet."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"R97","DOI":"10.1093\/hmg\/dds346","article-title":"COL4A1 and COL4A2 mutations and disease: Insights into pathogenic mechanisms and potential therapeutic targets","volume":"21","author":"Kuo","year":"2012","journal-title":"Hum. Mol. Genet."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"784","DOI":"10.1038\/nchembio.1038","article-title":"Peroxidasin forms sulfilimine chemical bonds using hypohalous acids in tissue genesis","volume":"8","author":"Bhave","year":"2012","journal-title":"Nat. Chem. Biol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"3603","DOI":"10.1242\/dev.049189","article-title":"The C. elegans peroxidasin PXN-2 is essential for embryonic morphogenesis and inhibits adult axon regeneration","volume":"137","author":"Gotenstein","year":"2010","journal-title":"Development"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1073\/pnas.1318499111","article-title":"A unique covalent bond in basement membrane is a primordial innovation for tissue evolution","volume":"111","author":"Fidler","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/j.matbio.2016.07.012","article-title":"Cell therapy for basement membrane-linked diseases","volume":"57\u201358","author":"Nystrom","year":"2017","journal-title":"Matrix Biol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1016\/j.ajhg.2011.08.005","article-title":"Homozygous mutations in PXDN cause congenital cataract, corneal opacity, and developmental glaucoma","volume":"89","author":"Khan","year":"2011","journal-title":"Am. J. Hum. Genet."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1038\/ejhg.2014.119","article-title":"Novel mutations in PXDN cause microphthalmia and anterior segment dysgenesis","volume":"23","author":"Choi","year":"2015","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"5597","DOI":"10.1093\/hmg\/ddu274","article-title":"Peroxidasin is essential for eye development in the mouse","volume":"23","author":"Yan","year":"2014","journal-title":"Hum. Mol. Genet."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"725","DOI":"10.2353\/ajpath.2009.080693","article-title":"Peroxidasin is secreted and incorporated into the extracellular matrix of myofibroblasts and fibrotic kidney","volume":"175","author":"Peterfi","year":"2009","journal-title":"Am. J. Pathol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2619","DOI":"10.1681\/ASN.2018050519","article-title":"Inhibitory Anti-Peroxidasin Antibodies in Pulmonary-Renal Syndromes","volume":"29","author":"McCall","year":"2018","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1016\/j.tibs.2014.05.005","article-title":"Peroxidasins: Novel players in tissue genesis","volume":"39","author":"Peterfi","year":"2014","journal-title":"Trends Biochem. Sci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/j.freeradbiomed.2015.02.015","article-title":"Structure-function analysis of peroxidasin provides insight into the mechanism of collagen IV crosslinking","volume":"83","author":"Lazar","year":"2015","journal-title":"Free Radic. Biol. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"21741","DOI":"10.1074\/jbc.M115.673996","article-title":"The Ancient Immunoglobulin Domains of Peroxidasin Are Required to Form Sulfilimine Cross-links in Collagen IV","volume":"290","author":"Hudson","year":"2015","journal-title":"J. Biol. Chem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"R82","DOI":"10.1186\/gb-2013-14-7-r82","article-title":"A comparative phenotypic and genomic analysis of C57BL\/6J and C57BL\/6N mouse strains","volume":"14","author":"Simon","year":"2013","journal-title":"Genome Biol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1016\/S1050-1738(96)00110-7","article-title":"Pax3, neural crest and cardiovascular development","volume":"6","author":"Epstein","year":"1996","journal-title":"Trends Cardiovasc. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1016\/S0070-2153(10)90010-0","article-title":"Eye development","volume":"90","author":"Graw","year":"2010","journal-title":"Curr. Top. Dev. Biol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.exer.2008.08.002","article-title":"The lens capsule","volume":"88","author":"Danysh","year":"2009","journal-title":"Exp. Eye Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1016\/j.matbio.2009.02.004","article-title":"Developmental distribution of collagen IV isoforms and relevance to ocular diseases","volume":"28","author":"Bai","year":"2009","journal-title":"Matrix Biol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"F596","DOI":"10.1152\/ajprenal.00096.2017","article-title":"The sulfilimine cross-link of collagen IV contributes to kidney tubular basement membrane stiffness","volume":"313","author":"Bhave","year":"2017","journal-title":"Am. J. Physiol. Renal Physiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1007\/s00439-019-01995-w","article-title":"Mouse models for microphthalmia, anophthalmia and cataracts","volume":"138","author":"Graw","year":"2019","journal-title":"Hum. Genet."},{"key":"ref_29","first-page":"95","article-title":"Small eyes (Sey): A homozygous lethal mutation on chromosome 2 which affects the differentiation of both lens and nasal placodes in the mouse","volume":"97","author":"Hogan","year":"1986","journal-title":"J. Embryol. Exp. Morphol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1041","DOI":"10.1002\/bies.10174","article-title":"Pax6; a pleiotropic player in development","volume":"24","author":"Simpson","year":"2002","journal-title":"Bioessays"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1016\/S0006-291X(03)00656-9","article-title":"Inhibition of endothelial cell proliferation by the recombinant kringle domain of tissue-type plasminogen activator","volume":"304","author":"Kim","year":"2003","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1016\/j.redox.2018.03.009","article-title":"Peroxidasin-mediated crosslinking of collagen IV is independent of NADPH oxidases","volume":"16","author":"Sirokmany","year":"2018","journal-title":"Redox Biol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/20\/24\/6144\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:40:41Z","timestamp":1760190041000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/20\/24\/6144"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,12,5]]},"references-count":32,"journal-issue":{"issue":"24","published-online":{"date-parts":[[2019,12]]}},"alternative-id":["ijms20246144"],"URL":"https:\/\/doi.org\/10.3390\/ijms20246144","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,12,5]]}}}