{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T06:09:52Z","timestamp":1761718192839},"reference-count":34,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2012,4,26]],"date-time":"2012-04-26T00:00:00Z","timestamp":1335398400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatism"],"published-print":{"date-parts":[[2012,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Mutations in matrilin 3 can result in multiple epiphyseal dysplasia (MED), a disease characterized by delayed and irregular bone growth and early\u2010onset osteoarthritis. Although intracellular retention of the majority of mutant matrilin 3 was previously observed in a murine model of MED caused by a <jats:italic>Matn3<\/jats:italic> V194D mutation, some mutant protein was secreted into the extracellular matrix. Thus, it was proposed that secretion of mutant matrilin 3 may be dependent on the formation of hetero\u2010oligomers with matrilin 1. The aim of this study was to investigate the hypothesis that deletion of matrilin 1 would abolish the formation of matrilin 1\/matrilin 3 hetero\u2010oligomers, eliminate the secretion of mutant matrilin 3, and influence disease severity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Mice with a <jats:italic>Matn3<\/jats:italic> V194D mutation were crossed with <jats:italic>Matn1<\/jats:italic>\u2010null mice, generating mice that were homozygous for V194D and null for matrilin 1. This novel mouse was used for in\u2010depth phenotyping, while cartilage and chondrocytes were studied both histochemically and biochemically.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Endochondral ossification was not disrupted any further in mice with a double V194D mutation compared with mice with a single mutation. A similar proportion of mutant matrilin 3 was present in the extracellular matrix, and the amount of retained mutant matrilin 3 was not noticeably increased. Retained mutant matrilin 3 formed disulfide\u2010bonded aggregates and caused the co\u2010retention of matrilin 1.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>We showed that secretion of matrilin 3 V194D mutant protein is not dependent on hetero\u2010oligomerization with matrilin 1, and that the total ablation of matrilin 1 expression has no impact on disease severity in mice with MED. Mutant matrilin 3 oligomers form non\u2010native disulfide\u2010bonded aggregates through the misfolded A domain.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.33486","type":"journal-article","created":{"date-parts":[[2011,11,14]],"date-time":"2011-11-14T16:13:12Z","timestamp":1321287192000},"page":"1529-1539","source":"Crossref","is-referenced-by-count":7,"title":["Loss of matrilin 1 does not exacerbate the skeletal phenotype in a mouse model of multiple epiphyseal dysplasia caused by a <i>Matn3<\/i> V194D mutation"],"prefix":"10.1002","volume":"64","author":[{"given":"Peter A.","family":"Bell","sequence":"first","affiliation":[]},{"given":"Katarzyna A.","family":"Pir\u00f3g","sequence":"additional","affiliation":[]},{"given":"Maryline","family":"Fresquet","sequence":"additional","affiliation":[]},{"given":"David J.","family":"Thornton","sequence":"additional","affiliation":[]},{"given":"Raymond P.","family":"Boot\u2010Handford","sequence":"additional","affiliation":[]},{"given":"Michael D.","family":"Briggs","sequence":"additional","affiliation":[]}],"member":"311","published-online":{"date-parts":[[2012,4,26]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.31483"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1086\/377110"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.berh.2007.11.009"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/humu.10066"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/humu.21611"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2005.03.018"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M705301200"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.matbio.2007.11.007"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.24979"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.25.23.10465-10478.2005"},{"key":"e_1_2_6_12_2","first-page":"1067","article-title":"Genetic mouse models for the functional analysis of the perifibrillar components collagen IX, COMP and matrilin 3: implications for growth cartilage differentiation and endochondral ossification","volume":"24","author":"Zaucke F","year":"2009","journal-title":"Histol Histopathol"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M009507200"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.154443"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0945-053X(98)00006-7"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1002\/humu.20263"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng573"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2003.011429"},{"key":"e_1_2_6_19_2","doi-asserted-by":"publisher","DOI":"10.1002\/humu.9286"},{"key":"e_1_2_6_20_2","doi-asserted-by":"publisher","DOI":"10.1002\/humu.9518"},{"key":"e_1_2_6_21_2","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2004.029462"},{"key":"e_1_2_6_22_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddm121"},{"key":"e_1_2_6_23_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12192-010-0193-y"},{"key":"e_1_2_6_24_2","doi-asserted-by":"publisher","DOI":"10.1006\/abbi.2000.2256"},{"key":"e_1_2_6_25_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.28.17433"},{"key":"e_1_2_6_26_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M202146200"},{"key":"e_1_2_6_27_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.275.6.3999"},{"key":"e_1_2_6_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2007.01.026"},{"key":"e_1_2_6_29_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddm155"},{"key":"e_1_2_6_30_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1000691"},{"key":"e_1_2_6_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0945-053X(98)90020-8"},{"key":"e_1_2_6_32_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.19.11.7841"},{"key":"e_1_2_6_33_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M610994200"},{"key":"e_1_2_6_34_2","doi-asserted-by":"publisher","DOI":"10.1002\/humu.21631"},{"key":"e_1_2_6_35_2","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.20486"}],"container-title":["Arthritis &amp; 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