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Mice heterozygous for\n            <jats:italic>Ext1<\/jats:italic>\n            or\n            <jats:italic>Ext2<\/jats:italic>\n            , modeling the human genotypes that cause MO, occasionally develop solitary osteochondroma-like structures on ribs [Lin et al. (2000)\n            <jats:italic>Dev Biol<\/jats:italic>\n            224(2):299\u2013311; Stickens et al. (2005)\n            <jats:italic>Development<\/jats:italic>\n            132(22):5055\u20135068]. Rather than model the germ-line genotype, we modeled the chimeric tissue genotype of somatic loss of heterozygosity (LOH), by conditionally inactivating\n            <jats:italic>Ext1<\/jats:italic>\n            via head-to-head\n            <jats:italic>loxP<\/jats:italic>\n            sites and temporally controlled\n            <jats:italic>Cre<\/jats:italic>\n            -recombinase in chondrocytes. These mice faithfully recapitulate the human phenotype of multiple metaphyseal osteochondromas. We also confirm homozygous disruption of\n            <jats:italic>Ext1<\/jats:italic>\n            in osteochondroma chondrocytes and their origin in proliferating physeal chondrocytes. These results explain prior modeling failures with the necessity for somatic LOH in a developmentally regulated cell type.\n          <\/jats:p>","DOI":"10.1073\/pnas.0910875107","type":"journal-article","created":{"date-parts":[[2009,12,23]],"date-time":"2009-12-23T02:09:29Z","timestamp":1261534169000},"page":"2054-2059","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":112,"title":["A mouse model of osteochondromagenesis from clonal inactivation of\n            <i>Ext1<\/i>\n            in chondrocytes"],"prefix":"10.1073","volume":"107","author":[{"given":"Kevin B.","family":"Jones","sequence":"first","affiliation":[{"name":"Department of Orthopaedics, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112;"},{"name":"Department of Orthopaedics and Rehabilitation, University of Iowa, Iowa City, IA 52242;"}]},{"given":"Virginia","family":"Piombo","sequence":"additional","affiliation":[{"name":"Developmental Biology I, Center for Medical Biotechnology, Department for Biology and Geography, University of Duisburg-Essen, D-45117 Essen, Germany;"}]},{"given":"Charles","family":"Searby","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Medical Genetics, Howard Hughes Medical Institute, University of Iowa, Iowa City, IA 52242;"}]},{"given":"Gail","family":"Kurriger","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics and Rehabilitation, University of Iowa, Iowa City, IA 52242;"}]},{"given":"Baoli","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, University of Iowa, Iowa City, IA 52242;"}]},{"given":"Florian","family":"Grabellus","sequence":"additional","affiliation":[{"name":"Institute for Pathology and Neuropathology, University Hospital Essen, D-45122 Essen, Germany;"}]},{"given":"Peter J.","family":"Roughley","sequence":"additional","affiliation":[{"name":"Genetics Unit, Shriner\u2019s Hospital, Montreal, Quebec H3G 1A6, Canada; and"}]},{"given":"Jose A.","family":"Morcuende","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics and Rehabilitation, University of Iowa, Iowa City, IA 52242;"}]},{"given":"Joseph A.","family":"Buckwalter","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics and Rehabilitation, University of Iowa, Iowa City, IA 52242;"}]},{"given":"Mario R.","family":"Capecchi","sequence":"additional","affiliation":[{"name":"Department of Human Genetics and Howard Hughes Medical Institute, University of Utah, Salt Lake City, UT 84112"}]},{"given":"Andrea","family":"Vortkamp","sequence":"additional","affiliation":[{"name":"Developmental Biology I, Center for Medical Biotechnology, Department for Biology and Geography, University of Duisburg-Essen, D-45117 Essen, Germany;"}]},{"given":"Val C.","family":"Sheffield","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Medical Genetics, Howard Hughes Medical Institute, University of Iowa, Iowa City, IA 52242;"}]}],"member":"341","published-online":{"date-parts":[[2010,1,8]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320550113"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1172-3-3"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1095-137"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-8628(19980217)75:5<538::AID-AJMG17>3.0.CO;2-L"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1086\/301726"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1080\/15216540214928"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.97.2.668"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1093\/embo-reports\/kvd045"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.01061"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-9896(199906)188:2<119::AID-PATH321>3.0.CO;2-N"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.68.4.820"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0169(200102)48:2<149::AID-CM1005>3.0.CO;2-3"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1086\/302532"},{"key":"e_1_3_3_14_2","first-page":"1125","article-title":"Hereditary multiple exostosis and chondrosarcoma: Linkage to chromosome II and loss of heterozygosity for EXT-linked markers on chromosomes II and 8","volume":"56","author":"Hecht JT","year":"1995","unstructured":"JT Hecht, et al., Hereditary multiple exostosis and chondrosarcoma: Linkage to chromosome II and loss of heterozygosity for EXT-linked markers on chromosomes II and 8. 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