{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T14:11:52Z","timestamp":1780323112180,"version":"3.54.1"},"reference-count":26,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,1,24]],"date-time":"2025-01-24T00:00:00Z","timestamp":1737676800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82101937"],"award-info":[{"award-number":["82101937"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Anim Models and Exp Med"],"published-print":{"date-parts":[[2025,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Makorin ring finger protein 3 gene (<jats:italic>MKRN3<\/jats:italic>) gene mutation is the most common genetic cause of central precocious puberty (CPP) in children. Due to the lack of ideal <jats:italic>MKRN3<\/jats:italic>\u2010modified animal model (<jats:italic>MKRN3<\/jats:italic>\u2010modified mice enter puberty only 4\u20135\u2009days earlier than normal mice), the related research is limited.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Therefore, the <jats:italic>MKRN3<\/jats:italic>\u2010modified rabbit was developed using CRISPR (clustered regularly interspaced short palindromic repeats) gene editing technology. The genotype identification and phenotype evaluation of <jats:italic>MKRN3<\/jats:italic>\u2010modified rabbits were carried out.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The first estrus of <jats:italic>MKRN3<\/jats:italic>\u2010modified female rabbits was observed ~27\u2009days earlier than that of wild\u2010type female rabbits, with a typical CPP phenotype. This study found increased gonadotropin releasing hormone (GnRH) and decreased gonadotropin inhibiting hormone (GnIH) in the hypothalamus of the CPP rabbit model with MKRN3 gene mutation. Although this study failed to fully clarify the pathogenesis of CPP caused by <jats:italic>MKRN3<\/jats:italic> mutation, it found some differentially expressed genes and potential pathways through transcriptome sequencing.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This study established a novel CPP model: paternal <jats:italic>MKRN3<\/jats:italic> gene\u2010modified rabbit. It is hoped that the establishment of this model will help researchers better understand, treat, and prevent CPP in the future.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ame2.12544","type":"journal-article","created":{"date-parts":[[2025,1,24]],"date-time":"2025-01-24T10:45:32Z","timestamp":1737715532000},"page":"511-522","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["A novel model of central precocious puberty disease: Paternal <scp><i>MKRN3<\/i><\/scp> gene\u2013modified rabbit"],"prefix":"10.1002","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2526-9551","authenticated-orcid":false,"given":"Bangzhu","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, Guangdong Provincial Key Laboratory of Major Obstetric Diseases, Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology, Guangdong\u2010Hong Kong\u2010Macao Greater Bay Area Higher Education Joint Laboratory of Maternal\u2010Fetal Medicine The Third Affiliated Hospital, Guangzhou Medical University  Guangzhou China"},{"name":"Guangdong Medical Laboratory Animal Center Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xing","family":"Ye","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences Southern Medical University  Guangzhou China"},{"name":"Institute of Comparative Medicine and Laboratory Animal Center Southern Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lihao","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Guangdong Provincial Key Laboratory of Major Obstetric Diseases, Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology, Guangdong\u2010Hong Kong\u2010Macao Greater Bay Area Higher Education Joint Laboratory of Maternal\u2010Fetal Medicine The Third Affiliated Hospital, Guangzhou Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianping","family":"Liu","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Large Animal Models for Biomedicine, School of Pharmacy and Food Engineering Wuyi University  Jiangmen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guiling","family":"Li","sequence":"additional","affiliation":[{"name":"Guangdong Medical Laboratory Animal Center Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chula","family":"Sa","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Large Animal Models for Biomedicine, School of Pharmacy and Food Engineering 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