{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T16:52:56Z","timestamp":1793206376316,"version":"4.5.0"},"reference-count":74,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2024,1,27]],"date-time":"2024-01-27T00:00:00Z","timestamp":1706313600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"University of Otago Research Grant"},{"DOI":"10.13039\/100008247","name":"University of Otago","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008247","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,4,18]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Adolescent idiopathic scoliosis (AIS) is the most common form of scoliosis, in which spinal curvature develops in adolescence, and 90% of patients are female. Scoliosis is a debilitating disease that often requires bracing or surgery in severe cases. AIS affects 2%\u20135.2% of the population; however, the biological origin of the disease remains poorly understood. In this study, we aimed to determine the function of a highly conserved genomic region previously linked to AIS using a mouse model generated by CRISPR-CAS9 gene editing to knockout this area of the genome to understand better its contribution to AIS, which we named AIS_CRM\u0394. We also investigated the upstream factors that regulate the activity of this enhancer in vivo, whether the spatial expression of the LBX1 protein would change with the loss of AIS-CRM function, and whether any phenotype would arise after deletion of this region. We found a significant increase in mRNA expression in the developing neural tube at E10.5, and E12.5, for not only Lbx1 but also other neighboring genes. Adult knockout mice showed vertebral rotation and proprioceptive deficits, also observed in human AIS patients. In conclusion, our study sheds light on the elusive biological origins of AIS, by targeting and investigating a highly conserved genomic region linked to AIS in humans. These findings provide valuable insights into the function of the investigated region and contribute to our understanding of the underlying causes of this debilitating disease.<\/jats:p>","DOI":"10.1093\/hmg\/ddae011","type":"journal-article","created":{"date-parts":[[2024,1,15]],"date-time":"2024-01-15T08:19:22Z","timestamp":1705306762000},"page":"787-801","source":"Crossref","is-referenced-by-count":6,"title":["Deletion of a conserved genomic region associated with adolescent idiopathic scoliosis leads to vertebral rotation in mice"],"prefix":"10.1093","volume":"33","author":[{"given":"Jeremy","family":"McCallum-Loudeac","sequence":"first","affiliation":[{"name":"Department of Anatomy , School of Biomedical Sciences, , P.O. Box 56, Dunedin 9054 , New Zealand"},{"name":"University of Otago , School of Biomedical Sciences, , P.O. Box 56, Dunedin 9054 , New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward","family":"Moody","sequence":"additional","affiliation":[{"name":"Department of Anatomy , School of Biomedical Sciences, , P.O. Box 56, Dunedin 9054 , New Zealand"},{"name":"University of Otago , School of Biomedical Sciences, , P.O. Box 56, Dunedin 9054 , New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jack","family":"Williams","sequence":"additional","affiliation":[{"name":"Department of Anatomy , School of Biomedical Sciences, , P.O. Box 56, Dunedin 9054 , New Zealand"},{"name":"University of Otago , School of Biomedical Sciences, , P.O. Box 56, Dunedin 9054 , New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georgia","family":"Johnstone","sequence":"additional","affiliation":[{"name":"Department of Anatomy , School of Biomedical Sciences, , P.O. Box 56, Dunedin 9054 , New Zealand"},{"name":"University of Otago , School of Biomedical Sciences, , P.O. Box 56, Dunedin 9054 , New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathleen J","family":"Sircombe","sequence":"additional","affiliation":[{"name":"Department of Anatomy , School of Biomedical Sciences, , P.O. Box 56, Dunedin 9054 , New Zealand"},{"name":"University of Otago , School of Biomedical Sciences, , P.O. Box 56, Dunedin 9054 , New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew N","family":"Clarkson","sequence":"additional","affiliation":[{"name":"Department of Anatomy , School of Biomedical Sciences, , P.O. Box 56, Dunedin 9054 , New Zealand"},{"name":"University of Otago , School of Biomedical Sciences, , P.O. Box 56, Dunedin 9054 , New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3425-5071","authenticated-orcid":false,"given":"Megan J","family":"Wilson","sequence":"additional","affiliation":[{"name":"Department of Anatomy , School of Biomedical Sciences, , P.O. Box 56, Dunedin 9054 , New Zealand"},{"name":"University of Otago , School of Biomedical Sciences, , P.O. Box 56, Dunedin 9054 , New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,1,27]]},"reference":[{"key":"2024042000555737200_ref1","doi-asserted-by":"crossref","first-page":"1527","DOI":"10.1016\/S0140-6736(08)60658-3","article-title":"Adolescent idiopathic scoliosis","volume":"371","author":"Weinstein","year":"2008","journal-title":"Lancet"},{"key":"2024042000555737200_ref2","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1590\/S1413-78522013000400008","article-title":"Epidemiologia da escoliose idiop\u00e1tica do adolescente em alunos da rede p\u00fablica de Goi\u00e2nia-GO","volume":"21","author":"Souza","year":"2013","journal-title":"Acta Ortop Bras"},{"key":"2024042000555737200_ref3","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1038\/s41413-020-0089-0","article-title":"The cartilage matrisome in adolescent idiopathic 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