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We created a mouse model of LMS (<jats:italic>Notch3<\/jats:italic><jats:sup><jats:italic>tm1.1Ecan<\/jats:italic><\/jats:sup>) by introducing a tandem termination codon in the <jats:italic>Notch3<\/jats:italic> locus upstream of the proline (P), glutamic acid (E), serine (S) and threonine (T) domain. Microcomputed tomography demonstrated that <jats:italic>Notch3<\/jats:italic><jats:sup><jats:italic>tm1.1Ecan<\/jats:italic><\/jats:sup> mice exhibit osteopenia. The cancellous bone osteopenia was no longer observed after the intraperitoneal administration of antibodies directed to the negative regulatory region (NRR) of Notch3. The anti\u2010Notch3 NRR antibody suppressed the expression of <jats:italic>Hes1<\/jats:italic>, <jats:italic>Hey1<\/jats:italic>, and <jats:italic>Hey2<\/jats:italic> (Notch target genes), and decreased <jats:italic>Tnfsf11<\/jats:italic> (receptor activator of NF Kappa B ligand) messenger RNA in <jats:italic>Notch3<\/jats:italic><jats:sup><jats:italic>tm1.1Ecan<\/jats:italic><\/jats:sup> osteoblast (OB) cultures. Bone marrow\u2010derived macrophages (BMMs) from <jats:italic>Notch3<\/jats:italic><jats:sup><jats:italic>tm1.1Ecan<\/jats:italic><\/jats:sup> mutants exhibited enhanced osteoclastogenesis in culture, and this was increased in cocultures with <jats:italic>Notch3<\/jats:italic><jats:sup><jats:italic>tm1.1Ecan<\/jats:italic><\/jats:sup> OB. Osteoclastogenesis was suppressed by anti\u2010Notch3 NRR antibodies in <jats:italic>Notch3<\/jats:italic><jats:sup><jats:italic>tm1.1Ecan<\/jats:italic><\/jats:sup> OB\/BMM cocultures. In conclusion, the cancellous bone osteopenia of <jats:italic>Notch3<\/jats:italic><jats:sup><jats:italic>tm1.1Ecan<\/jats:italic><\/jats:sup> mutants is reversed by anti\u2010Notch3 NRR antibodies.<\/jats:p>","DOI":"10.1002\/jcp.28960","type":"journal-article","created":{"date-parts":[[2019,6,12]],"date-time":"2019-06-12T12:36:30Z","timestamp":1560342990000},"page":"210-220","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["An antibody to Notch3 reverses the skeletal phenotype of lateral meningocele syndrome in male mice"],"prefix":"10.1002","volume":"235","author":[{"given":"Jungeun","family":"Yu","sequence":"first","affiliation":[{"name":"Department of Orthopaedic Surgery UConn Health Farmington Connecticut"},{"name":"The UConn Musculoskeletal Institute UConn Health Farmington Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian W.","family":"Siebel","sequence":"additional","affiliation":[{"name":"Department of Discovery Oncology Genentech, Inc South San Francisco California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren","family":"Schilling","sequence":"additional","affiliation":[{"name":"The UConn Musculoskeletal Institute UConn Health Farmington Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9154-952X","authenticated-orcid":false,"given":"Ernesto","family":"Canalis","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery UConn Health Farmington Connecticut"},{"name":"The UConn Musculoskeletal Institute UConn Health Farmington Connecticut"},{"name":"Department of Medicine UConn Health Farmington Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,6,12]]},"reference":[{"key":"e_1_2_9_1_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.33510"},{"key":"e_1_2_9_1_3_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M707000200"},{"key":"e_1_2_9_1_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.141"},{"key":"e_1_2_9_1_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00198-018-4694-3"},{"key":"e_1_2_9_1_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.24625"},{"key":"e_1_2_9_1_7_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2016-1787"},{"key":"e_1_2_9_1_8_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M115.685453"},{"key":"e_1_2_9_1_9_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.RA118.004242"},{"key":"e_1_2_9_1_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.25859"},{"key":"e_1_2_9_1_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2014.04.028"},{"key":"e_1_2_9_1_12_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-16-1022"},{"key":"e_1_2_9_1_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2015.10.006"},{"key":"e_1_2_9_1_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2009.03.010"},{"key":"e_1_2_9_1_15_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.00299-08"},{"key":"e_1_2_9_1_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.1318"},{"key":"e_1_2_9_1_17_1","doi-asserted-by":"publisher","DOI":"10.1359\/jbmr.070507"},{"key":"e_1_2_9_1_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2015.05.004"},{"key":"e_1_2_9_1_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.36863"},{"key":"e_1_2_9_1_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-8628(19970613)70:3<229::AID-AJMG4>3.0.CO;2-R"},{"key":"e_1_2_9_1_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2013.02.020"},{"key":"e_1_2_9_1_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.10208"},{"key":"e_1_2_9_1_23_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.21.17.6071-6079.2001"},{"key":"e_1_2_9_1_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-405943-6.00007-5"},{"key":"e_1_2_9_1_25_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2164-8-127"},{"key":"e_1_2_9_1_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2008.223"},{"key":"e_1_2_9_1_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2013.03.001"},{"issue":"12","key":"e_1_2_9_1_28_1","first-page":"1403","article-title":"v\u2010ATPase V0 subunit d2\u2010deficient mice exhibit impaired osteoclast fusion and increased bone formation","volume":"12","author":"Lee S. 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