{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T21:47:12Z","timestamp":1775598432417,"version":"3.50.1"},"reference-count":32,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2015,8,10]],"date-time":"2015-08-10T00:00:00Z","timestamp":1439164800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"NIH","award":["R01DE020843"],"award-info":[{"award-number":["R01DE020843"]}]},{"name":"NIH","award":["ES071003-11"],"award-info":[{"award-number":["ES071003-11"]}]},{"name":"NIH","award":["R01DE013085"],"award-info":[{"award-number":["R01DE013085"]}]},{"name":"NIH","award":["R01DE019527"],"award-info":[{"award-number":["R01DE019527"]}]},{"name":"\u03bcCT core at the School of Dentistry, University of Michigan"},{"name":"NIH\/NCRR","award":["S10RR026475"],"award-info":[{"award-number":["S10RR026475"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genesis"],"published-print":{"date-parts":[[2015,9]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Ellis\u2010van Creveld (EvC) syndrome (OMIM 225500) is an autosomal recessive disease characterized with chondrodysplastic dwarfism in association with abnormalities in oral cavity. Ciliary proteins EVC and EVC2 have been identified as causative genes and they play an important role on Hedgehog signal transduction. We have also identified a causative gene <jats:italic>LIMBIN<\/jats:italic> for bovine chondrodysplastic dwarfism (<jats:italic>bcd<\/jats:italic>) that is later identified as the bovine ortholog of <jats:italic>EVC2<\/jats:italic>. Here, we report generation of conventional and conditional mutant <jats:italic>Evc2<\/jats:italic>\/<jats:italic>Limbin<\/jats:italic> alleles that mimics mutations found in EvC patients and <jats:italic>bcd<\/jats:italic> cattle. Resulted homozygous mice showed no ciliary localization of EVC2 and EVC and displayed reduced Hedgehog signaling activity in association with skeletal and oral defects similar to the EvC patients. Cartilage\u2010specific disruption of <jats:italic>Evc2<\/jats:italic>\/<jats:italic>Limbin<\/jats:italic> resulted in similar but milder skeletal defects, whereas osteoblast\u2010specific disruption did not cause overt changes in skeletal system. Neural crest\u2010specific disruption of <jats:italic>Evc2<\/jats:italic>\/<jats:italic>Limbin<\/jats:italic> resulted in defective incisor growth similar to that seen in conventional knockouts; however, differentiation of amelobolasts was relatively normal in the conditional knockouts. These results showcased functions of EVC2\/LIMBIN during formation of mineralized tissues. Availability of the conditional allele for this gene should facilitate further detailed analyses of the role of EVC2\/LIMBIN in pathogenesis of EvC syndrome. genesis 53:612\u2013626, 2015. \u00a9 2015 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/dvg.22879","type":"journal-article","created":{"date-parts":[[2015,7,29]],"date-time":"2015-07-29T01:21:05Z","timestamp":1438132865000},"page":"612-626","source":"Crossref","is-referenced-by-count":28,"title":["Generation of <i>Evc2\/Limbin<\/i> global and conditional <scp>KO<\/scp> mice and its roles during mineralized tissue formation"],"prefix":"10.1002","volume":"53","author":[{"given":"Honghao","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Biologic and Materials Sciences School of Dentistry, University of Michigan  Michigan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haruko","family":"Takeda","sequence":"additional","affiliation":[{"name":"Reproductive and Developmental Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park  North Carolina"},{"name":"Unit of Animal Genomics, GIGA\u2010R &amp; Faculty of Veterinary Medicine, University of Li\u00e8ge 1 Avenue De L'h\u00f4pital Li\u00e8ge Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takehito","family":"Tsuji","sequence":"additional","affiliation":[{"name":"The Graduate School of Environment and Life Science, Okayama University Okayama City Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nobuhiro","family":"Kamiya","sequence":"additional","affiliation":[{"name":"Department of Biologic and Materials Sciences School of Dentistry, University of Michigan  Michigan"},{"name":"Reproductive and Developmental Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park  North Carolina"},{"name":"Faculty of Budo and Sport Studies, Tenri University Nara Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sudha","family":"Rajderkar","sequence":"additional","affiliation":[{"name":"Department of Biologic and Materials Sciences School of Dentistry, University of Michigan  Michigan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ke'Ale","family":"Louie","sequence":"additional","affiliation":[{"name":"Department of Biologic and Materials Sciences School of Dentistry, University of Michigan  Michigan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Crystal","family":"Collier","sequence":"additional","affiliation":[{"name":"College of Literature, Science and the Arts, University of Michigan  Michigan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Greg","family":"Scott","sequence":"additional","affiliation":[{"name":"Knock out Core, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park  North Carolina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manas","family":"Ray","sequence":"additional","affiliation":[{"name":"Knock out Core, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park  North Carolina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshiyuki","family":"Mochida","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cell Biology Henry M. Goldman School of Dental Medicine, Boston University 700 Albany Street Boston Massachusetts"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vesa","family":"Kaartinen","sequence":"additional","affiliation":[{"name":"Department of Biologic and Materials Sciences School of Dentistry, University of Michigan  Michigan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tetsuo","family":"Kunieda","sequence":"additional","affiliation":[{"name":"The Graduate School of Environment and Life Science, Okayama University Okayama City Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuji","family":"Mishina","sequence":"additional","affiliation":[{"name":"Department of Biologic and Materials Sciences School of Dentistry, University of Michigan  Michigan"},{"name":"Reproductive and Developmental Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park  North Carolina"},{"name":"Knock out Core, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park  North Carolina"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2015,8,10]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20011700"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.129.20.4753"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1172-2-27"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1186\/1741-7007-9-14"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/dds409"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2012.07.004"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/1526-968X(200011\/12)28:3\/4<106::AID-GENE30>3.0.CO;2-T"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.277.5329.1109"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.118802"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0925-4773(02)00292-7"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/dvg.20418"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.068833"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature01657"},{"key":"e_1_2_5_15_1","first-page":"306","article-title":"Dwarfism in the Amish I. 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