{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T08:59:57Z","timestamp":1773392397861,"version":"3.50.1"},"reference-count":65,"publisher":"American Physiological Society","issue":"4","funder":[{"DOI":"10.13039\/100000071","name":"HHS | NIH | National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["HD097559"],"award-info":[{"award-number":["HD097559"]}],"id":[{"id":"10.13039\/100000071","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"HHS | NIH | National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["GM125503"],"award-info":[{"award-number":["GM125503"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"HHS | NIH | National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["GM121293"],"award-info":[{"award-number":["GM121293"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006108","name":"HHS | NIH | National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","award":["TR001629"],"award-info":[{"award-number":["TR001629"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]},{"name":"University of Arkansas College of Medicine Research Scholar Pilot Grant Award"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Lung Cellular and Molecular Physiology"],"published-print":{"date-parts":[[2020,4,1]]},"abstract":"<jats:p> Respiratory disease is a leading cause of mortality in patients with osteogenesis imperfecta (OI), a connective tissue disease that causes severely reduced bone mass and is most commonly caused by dominant mutations in type I collagen genes. Previous studies proposed that impaired respiratory function in OI patients was secondary to skeletal deformities; however, recent evidence suggests the existence of a primary lung defect. Here, we analyzed the lung phenotype of Crtap knockout (KO) mice, a mouse model of recessive OI. While we confirm changes in the lung parenchyma that are reminiscent of emphysema, we show that CrtapKO lung fibroblasts synthesize type I collagen with altered posttranslation modifications consistent with those observed in bone and skin. Unrestrained whole body plethysmography showed a significant decrease in expiratory time, resulting in an increased ratio of inspiratory time over expiratory time and a concomitant increase of the inspiratory duty cycle in CrtapKO compared with WT mice. Closed-chest measurements using the forced oscillation technique showed increased respiratory system elastance, decreased respiratory system compliance, and increased tissue damping and elasticity in CrtapKO mice compared with WT. Pressure-volume curves showed significant differences in lung volumes and in the shape of the curves between CrtapKO mice and WT mice, with and without adjustment for body weight. This is the first evidence that collagen defects in OI cause primary changes in lung parenchyma and several respiratory parameters and thus negatively impact lung function. <\/jats:p>","DOI":"10.1152\/ajplung.00313.2019","type":"journal-article","created":{"date-parts":[[2020,2,5]],"date-time":"2020-02-05T16:05:18Z","timestamp":1580918718000},"page":"L592-L605","source":"Crossref","is-referenced-by-count":24,"title":["Respiratory defects in the <i>Crtap<\/i>KO mouse model of osteogenesis imperfecta"],"prefix":"10.1152","volume":"318","author":[{"given":"Milena","family":"Dimori","sequence":"first","affiliation":[{"name":"Department of Physiology & Biophysics, University of Arkansas for Medical Sciences, Little Rock, Arkansas"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Melissa E.","family":"Heard-Lipsmeyer","sequence":"additional","affiliation":[{"name":"Department of Physiology & Biophysics, University of Arkansas for Medical Sciences, Little Rock, Arkansas"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephanie D.","family":"Byrum","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, Little Rock, Arkansas"},{"name":"Arkansas Children\u2019s Research Institute, Little Rock, Arkansas"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samuel G.","family":"Mackintosh","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, Little Rock, Arkansas"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard C.","family":"Kurten","sequence":"additional","affiliation":[{"name":"Department of Physiology & Biophysics, University of Arkansas for Medical Sciences, Little Rock, Arkansas"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John L.","family":"Carroll","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, Arkansas"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1604-4879","authenticated-orcid":false,"given":"Roy","family":"Morello","sequence":"additional","affiliation":[{"name":"Department of Physiology & Biophysics, University of Arkansas for Medical Sciences, Little Rock, Arkansas"},{"name":"Department of Orthopaedic Surgery, University of Arkansas for Medical Sciences, Little Rock, Arkansas"},{"name":"Division of Genetics, University of Arkansas for Medical Sciences, Little Rock, Arkansas"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"24","reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.rmed.2017.07.063"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.4172\/2168-9547.1000150"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1590\/s1807-59322011001000020"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1038\/pr.2018.36"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0010560"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1002\/humu.20799"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00175-19"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa063804"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.7717\/peerj.2318"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1517\/21678707.2015.1006197"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.01805-2016"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2015.00027"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1000750"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1186\/s12931-017-0610-1"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1136\/thx.17.4.320"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.2895"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijcard.2016.09.107"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(15)00728-X"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1080\/019021490951522"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1186\/1465-9921-8-63"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.2000.89.3.908"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3544"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.90924.2008"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1992.72.1.168"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-62703-496-8_16"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1006002"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1016\/0034-5687(95)00068-2"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00884.2006"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2015-0166PS"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1136\/thx.41.6.418"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.3791\/52376"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.3791\/52964"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1002\/ppul.24039"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0035965"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2013-1505"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2017.52"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1136\/jcp.49.8.627"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.3791\/50172"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2006.08.039"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1007\/s11914-010-0010-7"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2004.03.008"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1021\/ac0341261"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00492.2016"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(04)16051-0"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1007\/s00335-002-3005-6"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkv007"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00856.2016"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1964.19.1.97"},{"key":"B49","first-page":"335","volume-title":"Osteogenesis Imperfecta: a Translational Approach to Brittle Bone Disease","author":"Sandhaus R","year":"2013"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1016\/8756-3282(89)90049-5"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(78)90763-8"},{"key":"B52","first-page":"113","volume":"15","author":"Sillence DO","year":"1979","journal-title":"Birth Defects Orig Artic Ser"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00596.2002"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1172\/JCI108037"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00048.2019"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1002\/cphy.c100033"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1002\/ppul.1950200508"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/dds183"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00587.2011"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.2011.01794.x"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2008-0487OC"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1016\/S0070-2153(10)90003-3"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1513\/AnnalsATS.201406-240MG"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1097\/00007632-199908150-00008"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1016\/j.matbio.2018.03.005"}],"container-title":["American Journal of Physiology-Lung Cellular and Molecular Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.physiology.org\/doi\/pdf\/10.1152\/ajplung.00313.2019","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,3,19]],"date-time":"2020-03-19T23:19:30Z","timestamp":1584659970000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.physiology.org\/doi\/10.1152\/ajplung.00313.2019"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,4,1]]},"references-count":65,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2020,4,1]]}},"alternative-id":["10.1152\/ajplung.00313.2019"],"URL":"https:\/\/doi.org\/10.1152\/ajplung.00313.2019","relation":{},"ISSN":["1040-0605","1522-1504"],"issn-type":[{"value":"1040-0605","type":"print"},{"value":"1522-1504","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,4,1]]}}}