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Previous genome\u2010wide association studies have identified a single\u2010nucleotide polymorphism (rs6137473) located downstream of\n                      <jats:italic>PAX1,<\/jats:italic>\n                      which is significantly associated with female AIS risk.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      To investigate the role of this region in spinal development and AIS pathogenesis, we generated a mouse model with deletion of a nearby conserved sex\u2010associated region (\n                      <jats:italic>Pax1<\/jats:italic>\n                      \u2010SAR\u0394). Spines were examined by both micro\u2010CT and histology. Gene expression analysis (by RNA\u2010sequencing and quantitative PCR) was carried out on E12.5 and E18.5 developing spines. Glycosaminoglycan (GAG) content was also measured by high\u2010performance liquid chromatography.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Micro\u2010CT analysis revealed increased vertebral rotation at T4 in female\n                      <jats:italic>Pax1<\/jats:italic>\n                      \u2010SAR\u0394 mice at 4\u2009months and at T9 in male\n                      <jats:italic>Pax1<\/jats:italic>\n                      \u2010SAR\u0394 mice at 6\u2009months, along with kyphotic and lordotic sagittal curvatures. Histological examination revealed significant intervertebral disc degeneration, with the most severe changes observed in the female\n                      <jats:italic>Pax1<\/jats:italic>\n                      \u2010SAR\u0394 mice. GAG analysis found decreased chondroitin sulfate and dermatan sulfate content in male and female\n                      <jats:italic>Pax1<\/jats:italic>\n                      \u2010SAR\u0394 mice. Gene expression analysis at E12.5 showed upregulation of\n                      <jats:italic>Pax1, Stat3, Ar<\/jats:italic>\n                      ,\n                      <jats:italic>Foxa2,<\/jats:italic>\n                      and\n                      <jats:italic>Nkx2.2<\/jats:italic>\n                      , while RNA\u2010sequencing at E18.5 revealed sex\u2010dependent changes in gene expression related to extracellular matrix components, immune and inflammatory responses, and scoliosis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      These findings highlight the pivotal role of the\n                      <jats:italic>Pax1<\/jats:italic>\n                      sex\u2010associated genomic region in the development and maintenance of functional cartilage, extracellular matrix integrity, and intervertebral disc health, offering insights into the mechanisms underlying spinal degeneration and instability in AIS.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jsp2.70177","type":"journal-article","created":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T01:36:08Z","timestamp":1776908168000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Deletion of a\n                    <i>Pax1<\/i>\n                    Sex\u2010Associated Genomic Region Associated With Adolescent Idiopathic Scoliosis Leads to Disc Degeneration, Instability, and Vertebral Rotation in Mice"],"prefix":"10.1002","volume":"9","author":[{"given":"Edward C.","family":"Moody","sequence":"first","affiliation":[{"name":"Developmental Genomics Laboratory, Department of Anatomy, Faculty of Biomedical Sciences University of Otago  Dunedin New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2990-0232","authenticated-orcid":false,"given":"Emma M.","family":"Wade","sequence":"additional","affiliation":[{"name":"Department of Obstetrics, Gynaecology and Women's Health, Dunedin School of Medicine University of Otago  Dunedin New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuji","family":"Mizumoto","sequence":"additional","affiliation":[{"name":"Department of Pathobiochemistry, Faculty of Pharmacy Meijo University  Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremy","family":"McCallum\u2010Loudeac","sequence":"additional","affiliation":[{"name":"Developmental Genomics Laboratory, Department of Anatomy, Faculty of Biomedical Sciences University of Otago  Dunedin 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":"Developmental Genomics Laboratory, Department of Anatomy, Faculty of Biomedical Sciences University of Otago  Dunedin New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,4,22]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/00007632\u2010198902000\u201000005"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/jsp2.1298"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469\u20107580.2012.01551.x"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.msec.2011.10.011"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.7326\/0003\u20104819\u2010147\u20105\u2010200709040\u201000008"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00586\u2010013\u20102903\u20105"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1227\/NEU.0000000000000938"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/jsp2.1076"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.inat.2019.100661"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13013\u2010016\u20100105\u20108"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/pch\/12.9.771"},{"key":"e_1_2_11_13_1","first-page":"111","article-title":"Adolescent Idiopathic Scoliosis: Review and Current Concepts","volume":"64","author":"Reamy B. 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