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.

Abstract

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.