DOI: 10.1002/ame2.12544
A novel model of central precocious puberty disease:Paternal MKRN3 gene-modified rabbit
Bangzhu Chen1
Xing Ye2
Lihao Chen3
Tianping Liu4
Guiling Li5
Chula Sa4
Juan Li5
Ke Liu5
Weiwang Gu4
Gang Wang5
1.Department 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,China;Guangdong Medical Laboratory Animal Center,Guangdong Provincial People's Hospital(Guangdong Academy of Medical Sciences),Southern Medical University,Guangzhou,China2.School of Basic Medical Sciences,Southern Medical University,Guangzhou,China;Institute of Comparative Medicine and Laboratory Animal Center,Southern Medical University,Guangzhou,China3.Department 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,China4.Guangdong Provincial Key Laboratory of Large Animal Models for Biomedicine,School of Pharmacy and Food Engineering,Wuyi University,Jiangmen,China5.Guangdong Medical Laboratory Animal Center,Guangdong Provincial People's Hospital(Guangdong Academy of Medical Sciences),Southern Medical University,Guangzhou,China
摘要：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(clus-tered 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～27days earlier than that of wild-type female rabbits,with a typical CPP phenotype.This study found increased gonadotropin releasing hormone(GnRH)and decreased gonado-tropin 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.
机标关键词：centralmkrn3rabbitnovelmodeldiseasegene-modifiedpaternal
论文发表日期：2025-03-30
在线出版日期：2025-08-15（本平台首次上网日期，不代表文献的发表时间）
页数：12( 511-522 )
英文信息