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A novel model of central precocious puberty disease: Paternal MKRN3 gene-modified rabbit
Bangzhu Chen1,2, Xing Ye3,4, Lihao Chen1
1Department 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.
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.
Insights
Researchers developed a new rabbit model for central precocious puberty (CPP) using MKRN3 gene editing. This model exhibits an earlier onset of puberty, aiding further CPP research.
Area of Science:
- Genetics and Developmental Biology
- Reproductive Endocrinology
- Animal Modeling
Background:
- Makorin ring finger protein 3 (MKRN3) gene mutations are the leading genetic cause of central precocious puberty (CPP) in children.
- Existing MKRN3-modified mouse models have limitations, hindering comprehensive research into CPP pathogenesis.
Purpose of the Study:
- To establish a more suitable animal model for studying MKRN3-associated central precocious puberty.
- To investigate the phenotype and genetic alterations in MKRN3-modified rabbits.
Main Methods:
- Utilized CRISPR gene editing technology to create MKRN3-modified rabbits.
- Conducted genotype identification and phenotype evaluation of the modified rabbits.
Main Results:
- MKRN3-modified female rabbits exhibited first estrus approximately 27 days earlier than wild-type rabbits, displaying a typical CPP phenotype.
- Observed increased gonadotropin-releasing hormone (GnRH) and decreased gonadotropin-inhibiting hormone (GnIH) in the hypothalamus of the CPP rabbit model.
- Transcriptome sequencing identified differentially expressed genes and potential pathways related to CPP.
Conclusions:
- Successfully established a novel rabbit model for central precocious puberty through paternal MKRN3 gene modification.
- This MKRN3-modified rabbit model is expected to advance the understanding, treatment, and prevention of CPP.

