{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T11:05:40Z","timestamp":1779361540706,"version":"3.51.4"},"reference-count":36,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T00:00:00Z","timestamp":1779321600000},"content-version":"vor","delay-in-days":140,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100005089","name":"Beijing Municipal Natural Science Foundation","doi-asserted-by":"publisher","award":["7244286"],"award-info":[{"award-number":["7244286"]}],"id":[{"id":"10.13039\/501100005089","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82000846"],"award-info":[{"award-number":["82000846"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81472053"],"award-info":[{"award-number":["81472053"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2022YFC2703700"],"award-info":[{"award-number":["2022YFC2703700"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Human Mutation"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:p>\n                    Osteogenesis imperfecta (OI) is a genetically and clinically heterogeneous bone disorder, with more than 20 genes contributing to OI development. Previously, we identified\n                    <jats:italic>WNT1<\/jats:italic>\n                    c.620G\u2009&gt;\u2009A (p.Arg207His) mutation among Chinese patients with autosomal recessive OI (AR\u2010OI). This study aims at investigating the causative role of\n                    <jats:italic>WNT1<\/jats:italic>\n                    deficiency in OI and evaluate whether AAV\u2010based gene therapy could ameliorate bone abnormalities. We generated and analyzed the Wnt1\n                    <jats:sup>R207H\/R207H<\/jats:sup>\n                    rat model. The AAV9\u2010Wnt1 virus was delivered via direct intraosseous injection into the femoral marrow cavity of the OI rats to evaluate its therapeutic potential. The homozygous Wnt1\n                    <jats:sup>R207H\/R207H<\/jats:sup>\n                    rat recapitulated key features of AR\u2010OI, including fractures, reduced bone mass, growth retardation, decreased survival rate, increased osteoclast numbers, diminished osteoblast function and mineralization capacity, compared with heterozygous and wild\u2010type littermates. In vitro,\n                    <jats:italic>Wnt1<\/jats:italic>\n                    overexpression in osteoblasts promoted osteoblast activity and bone mineralization. Furthermore, AAV9\u2010Wnt1 treatment in OI rats resulted in significant recovery of bone density and mechanical strength, stimulation of osteoblast activity, suppression of osteoclast activity, and upregulation of Type I collagen expression. Our study demonstrates that\n                    <jats:italic>WNT1<\/jats:italic>\n                    c.620G\u2009&gt;\u2009A (p.Arg207His) is pathogenic, and confirms that AAV\u2010mediated Wnt1 gene therapy represents a promising strategy for treating OI caused by\n                    <jats:italic>WNT1<\/jats:italic>\n                    mutations.\n                  <\/jats:p>","DOI":"10.1155\/humu\/7351808","type":"journal-article","created":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T10:12:39Z","timestamp":1779358359000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A New\n                    <i>Wnt1<\/i>\n                    Mutant Rat Model of Osteogenesis Imperfecta and Its Application in AAV9\u2010Mediated Gene Therapy"],"prefix":"10.1155","volume":"2026","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0272-6193","authenticated-orcid":false,"given":"Shan","family":"Li","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2107-5071","authenticated-orcid":false,"given":"Xiumin","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6025-637X","authenticated-orcid":false,"given":"Yixuan","family":"Cao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-1661-5822","authenticated-orcid":false,"given":"Mingchen","family":"Han","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1627-2452","authenticated-orcid":false,"given":"Feifei","family":"Guan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-3440-6285","authenticated-orcid":false,"given":"Xiuzhi","family":"Ren","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-2003-5040","authenticated-orcid":false,"given":"Huan","family":"Mi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9098-0134","authenticated-orcid":false,"given":"Tao","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7270-4902","authenticated-orcid":false,"given":"Mei","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8238-6311","authenticated-orcid":false,"given":"Xiuli","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,5,21]]},"reference":[{"key":"e_1_2_12_1_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/nrdp.2017.52","article-title":"Osteogenesis Imperfecta","volume":"3","author":"Marini J. C.","year":"2017","journal-title":"Nature Reviews. Disease Primers"},{"key":"e_1_2_12_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrendo.2011.81"},{"key":"e_1_2_12_3_2","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1055\/s-0036-1592372","article-title":"Skeletal Manifestations of Osteogenesis Imperfecta","volume":"20","author":"Fotiadou A.","year":"2016","journal-title":"Seminars in Musculoskeletal Radiology"},{"key":"e_1_2_12_4_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00223-012-9588-3"},{"key":"e_1_2_12_5_2","doi-asserted-by":"publisher","DOI":"10.1097\/MED.0000000000000367"},{"key":"e_1_2_12_6_2","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1136\/jmg.16.2.101","article-title":"Genetic Heterogeneity in Osteogenesis Imperfecta","volume":"16","author":"Sillence D. 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