{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T14:35:52Z","timestamp":1758810952303},"reference-count":51,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2015,7,1]],"date-time":"2015-07-01T00:00:00Z","timestamp":1435708800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>mua-3 is a Caenorhabditis elegans homolog of the mammalian fibrillin1, a monogenic cause of Marfan syndrome. We identified a new mutation of mua-3 that carries an in-frame deletion of 131 amino acids in the extracellular domain, which allows the mutants to survive in a temperature-dependent manner; at the permissive temperature, the mutants grow normally without obvious phenotypes, but at the nonpermissive temperature, more than 90% die during the L4 molt due to internal organ detachment. Using the temperature-sensitive lethality, we performed unbiased genetic screens to isolate suppressors to find genetic interactors of MUA-3. From two independent screens, we isolated mutations in dpy-17 as a suppressor. RNAi of dpy-17 in mua-3 rescued the lethality, confirming dpy-17 is a suppressor. dpy-17 encodes a collagen known to genetically interact with dpy-31, a BMP-1\/Tolloid-like metalloprotease required for TGF\u03b2 activation in mammals. Human fibrillin1 mutants fail to sequester TGF\u03b22 leading to excess TGF\u03b2 signaling, which in turn contributes to Marfan syndrome or Marfan-related syndrome. Consistent with that, RNAi of dbl-1, a TGF\u03b2 homolog, modestly rescued the lethality of mua-3 mutants, suggesting a potentially conserved interaction between MUA-3 and a TGF\u03b2 pathway in C. elegans. Our work provides genetic evidence of the interaction between TGF\u03b2 and a fibrillin homolog, and thus provides a simple yet powerful genetic model to study TGF\u03b2 function in development of Marfan pathology.<\/jats:p>","DOI":"10.1534\/g3.115.018465","type":"journal-article","created":{"date-parts":[[2015,5,1]],"date-time":"2015-05-01T17:26:38Z","timestamp":1430501198000},"page":"1371-1378","source":"Crossref","is-referenced-by-count":9,"title":["DPY-17 and MUA-3 Interact for Connective Tissue-Like Tissue Integrity in<i>Caenorhabditis elegans<\/i>: A Model for Marfan Syndrome"],"prefix":"10.1093","volume":"5","author":[{"given":"Pauline","family":"Fotopoulos","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Virginia Commonwealth University, Richmond, Virginia 23298"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeongho","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Inha University, Incheon, 402-751, South Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Moonjung","family":"Hyun","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Virginia Commonwealth University, Richmond, Virginia 23298"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Waiss","family":"Qamari","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Virginia Commonwealth University, Richmond, Virginia 23298"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Inhwan","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Virginia Commonwealth University, Richmond, Virginia 23298"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Young-Jai","family":"You","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Virginia Commonwealth University, Richmond, Virginia 23298"},{"name":"Department of Biochemistry and Molecular Biology, Virginia Commonwealth University, Richmond, Virginia 23298"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2015,7,1]]},"reference":[{"key":"2021042020035930500_bib1","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1093\/genetics\/133.4.897","article-title":"The genetics of feeding in Caenorhabditis elegans.","volume":"133","author":"Avery","year":"1993","journal-title":"Genetics"},{"key":"2021042020035930500_bib2","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1083\/jcb.200103035","article-title":"mua-3, a gene required for mechanical tissue integrity in Caenorhabditis elegans, encodes a novel transmembrane protein of epithelial attachment complexes.","volume":"154","author":"Bercher","year":"2001","journal-title":"J. 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