PUBLICATION
nr0b1 (DAX1) mutation in zebrafish causes female-to-male sex reversal through abnormal gonadal proliferation and differentiation
- Authors
- Chen, S., Zhang, H., Wang, F., Zhang, W., Peng, G.
- ID
- ZDB-PUB-160610-17
- 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.
Citation
Chen, S., Zhang, H., Wang, F., Zhang, W., Peng, G. (2016) nr0b1 (DAX1) mutation in zebrafish causes female-to-male sex reversal through abnormal gonadal proliferation and differentiation. Molecular and Cellular Endocrinology. 433:105-16.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping