A novel model of central precocious puberty disease: Paternal MKRN3 gene–modified rabbit
Abstract Background Makorin ring finger protein 3 gene (MKRN3) gene mutation is the most common genetic cause of central precocious puberty (CPP) in children. Due to the lack of ideal MKRN3‐modified animal model (MKRN3‐modified mice enter puberty only 4–5 days earlier than normal mice), the related...
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| Format: | Article |
| Language: | English |
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Wiley
2025-03-01
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| Series: | Animal Models and Experimental Medicine |
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| Online Access: | https://doi.org/10.1002/ame2.12544 |
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| author | Bangzhu Chen Xing Ye Lihao Chen Tianping Liu Guiling Li Chula Sa Juan Li Ke Liu Weiwang Gu Gang Wang |
| author_facet | Bangzhu Chen Xing Ye Lihao Chen Tianping Liu Guiling Li Chula Sa Juan Li Ke Liu Weiwang Gu Gang Wang |
| author_sort | Bangzhu Chen |
| collection | DOAJ |
| description | Abstract Background Makorin ring finger protein 3 gene (MKRN3) gene mutation is the most common genetic cause of central precocious puberty (CPP) in children. Due to the lack of ideal MKRN3‐modified animal model (MKRN3‐modified mice enter puberty only 4–5 days earlier than normal mice), the related research is limited. Methods Therefore, the MKRN3‐modified rabbit was developed using CRISPR (clustered regularly interspaced short palindromic repeats) gene editing technology. The genotype identification and phenotype evaluation of MKRN3‐modified rabbits were carried out. Results The first estrus of MKRN3‐modified female rabbits was observed ~27 days earlier than that of wild‐type 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 MKRN3 mutation, it found some differentially expressed genes and potential pathways through transcriptome sequencing. Conclusions This study established a novel CPP model: paternal MKRN3 gene‐modified rabbit. It is hoped that the establishment of this model will help researchers better understand, treat, and prevent CPP in the future. |
| format | Article |
| id | doaj-art-d6dcbdf81f944c9f9901c8ceec412270 |
| institution | OA Journals |
| issn | 2576-2095 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Wiley |
| record_format | Article |
| series | Animal Models and Experimental Medicine |
| spelling | doaj-art-d6dcbdf81f944c9f9901c8ceec4122702025-08-20T02:04:51ZengWileyAnimal Models and Experimental Medicine2576-20952025-03-018351152210.1002/ame2.12544A novel model of central precocious puberty disease: Paternal MKRN3 gene–modified rabbitBangzhu Chen0Xing Ye1Lihao Chen2Tianping Liu3Guiling Li4Chula Sa5Juan Li6Ke Liu7Weiwang Gu8Gang Wang9Department of Obstetrics and Gynecology, Guangdong Provincial Key Laboratory of Major Obstetric Diseases, Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology, Guangdong‐Hong Kong‐Macao Greater Bay Area Higher Education Joint Laboratory of Maternal‐Fetal Medicine The Third Affiliated Hospital, Guangzhou Medical University Guangzhou ChinaSchool of Basic Medical Sciences Southern Medical University Guangzhou ChinaDepartment of Obstetrics and Gynecology, Guangdong Provincial Key Laboratory of Major Obstetric Diseases, Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology, Guangdong‐Hong Kong‐Macao Greater Bay Area Higher Education Joint Laboratory of Maternal‐Fetal Medicine The Third Affiliated Hospital, Guangzhou Medical University Guangzhou ChinaGuangdong Provincial Key Laboratory of Large Animal Models for Biomedicine, School of Pharmacy and Food Engineering Wuyi University Jiangmen ChinaGuangdong Medical Laboratory Animal Center Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University Guangzhou ChinaGuangdong Provincial Key Laboratory of Large Animal Models for Biomedicine, School of Pharmacy and Food Engineering Wuyi University Jiangmen ChinaGuangdong Medical Laboratory Animal Center Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University Guangzhou ChinaGuangdong Medical Laboratory Animal Center Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University Guangzhou ChinaGuangdong Provincial Key Laboratory of Large Animal Models for Biomedicine, School of Pharmacy and Food Engineering Wuyi University Jiangmen ChinaGuangdong Medical Laboratory Animal Center Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University Guangzhou ChinaAbstract Background Makorin ring finger protein 3 gene (MKRN3) gene mutation is the most common genetic cause of central precocious puberty (CPP) in children. Due to the lack of ideal MKRN3‐modified animal model (MKRN3‐modified mice enter puberty only 4–5 days earlier than normal mice), the related research is limited. Methods Therefore, the MKRN3‐modified rabbit was developed using CRISPR (clustered regularly interspaced short palindromic repeats) gene editing technology. The genotype identification and phenotype evaluation of MKRN3‐modified rabbits were carried out. Results The first estrus of MKRN3‐modified female rabbits was observed ~27 days earlier than that of wild‐type 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 MKRN3 mutation, it found some differentially expressed genes and potential pathways through transcriptome sequencing. Conclusions This study established a novel CPP model: paternal MKRN3 gene‐modified rabbit. It is hoped that the establishment of this model will help researchers better understand, treat, and prevent CPP in the future.https://doi.org/10.1002/ame2.12544central precocious pubertygonadotropin inhibiting hormone (GnIH)gonadotropin releasing hormone (GnRH)MKRN3rabbit |
| spellingShingle | Bangzhu Chen Xing Ye Lihao Chen Tianping Liu Guiling Li Chula Sa Juan Li Ke Liu Weiwang Gu Gang Wang A novel model of central precocious puberty disease: Paternal MKRN3 gene–modified rabbit Animal Models and Experimental Medicine central precocious puberty gonadotropin inhibiting hormone (GnIH) gonadotropin releasing hormone (GnRH) MKRN3 rabbit |
| title | A novel model of central precocious puberty disease: Paternal MKRN3 gene–modified rabbit |
| title_full | A novel model of central precocious puberty disease: Paternal MKRN3 gene–modified rabbit |
| title_fullStr | A novel model of central precocious puberty disease: Paternal MKRN3 gene–modified rabbit |
| title_full_unstemmed | A novel model of central precocious puberty disease: Paternal MKRN3 gene–modified rabbit |
| title_short | A novel model of central precocious puberty disease: Paternal MKRN3 gene–modified rabbit |
| title_sort | novel model of central precocious puberty disease paternal mkrn3 gene modified rabbit |
| topic | central precocious puberty gonadotropin inhibiting hormone (GnIH) gonadotropin releasing hormone (GnRH) MKRN3 rabbit |
| url | https://doi.org/10.1002/ame2.12544 |
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