ZFIN ID: ZDB-PUB-160610-17
nr0b1 (DAX1) mutation in zebrafish causes female-to-male sex reversal through abnormal gonadal proliferation and differentiation
Chen, S., Zhang, H., Wang, F., Zhang, W., Peng, G.
Date: 2016
Source: Molecular and Cellular Endocrinology 433: 105-16 (Journal)
Registered Authors: Chen, Sijie, Peng, Gang, Wang, Fenghua, Zhang, Hefei, Zhang, Wei
Keywords: DAX1, Sex determination, Somatic cell, Zebrafish, nr0b1
MeSH Terms:
  • Animals
  • Caspase 3/genetics
  • Cell Differentiation/physiology*
  • Cell Proliferation/physiology*
  • DAX-1 Orphan Nuclear Receptor/genetics*
  • DNA-Binding Proteins/genetics
  • Disorders of Sex Development/genetics
  • Disorders of Sex Development/pathology
  • Female
  • Gonads/physiology*
  • Male
  • Mutation/genetics*
  • Ovary/physiology
  • Sex Determination Processes/genetics
  • Sex Differentiation/genetics
  • Testis/physiology
  • Tumor Suppressor Protein p53/genetics
  • Zebrafish/genetics*
  • Zebrafish/physiology*
PubMed: 27267667 Full text @ Mol. Cell. Endocrinol.
Sex determinations are diverse in vertebrates. Although many sex-determining genes and pathways are conserved, the mechanistic roles of these genes and pathways in the genetic sex determination are not well understood. DAX1 (encoded by the NR0B1 gene) is a vertebrate specific orphan nuclear receptor that regulates gonadal development and sexual determination. In human, duplication of the NR0B1 gene leads to male-to-female sex reversal. In mice, Nr0b1 shows both pro-testis and anti-testis functions. We generated inheritable nr0b1 mutation in the zebrafish and found the nr0b1 mutation caused homozygous mutants to develop as fertile males due to female-to-male sex reversal. The nr0b1 mutation did not increase Caspase-3 labeling nor tp53 expression in the developing gonads. Introduction of a tp53 mutation into the nr0b1 mutant did not rescue the sex-reversal phenotype. Further examination revealed reduction in cell proliferation and abnormal somatic cell differentiation in the nr0b1 mutant gonads at the undifferentiated and bi-potential ovary stages. Together, our results suggest nr0b1 regulates somatic cell differentiation and cell proliferation to ensure normal sex development in the zebrafish.