Mouse Dax1 expression is consistent with a role in sex determination as well as in adrenal and hypothalamus function

Nat Genet. 1996 Apr;12(4):404-9. doi: 10.1038/ng0496-404.


Duplications of a chromosome Xp21 locus DSS (Dosage Sensitive Sex reversal) are associated with male to female sex reversal. An unusual member of the nuclear hormone receptor superfamily, DAX1, maps to the DSS critical region and is responsible for X-linked adrenal hypoplasia congenita. Here we describe the isolation of the mouse Dax1 gene and its pattern of expression during development. Expression was detected in the first stages of gonadal and adrenal differentiation and in the developing hypothalamus. Moreover, Dax1 expression is down-regulated coincident with overt differentiation in the testis, but persists in the developing ovary. Comparison of the predicted protein products of the human and mouse genes show that specific domains are evolving rapidly. Our results suggest a basis for adrenal insufficiency and hypogonadotropic hypogonadism in males affected by adrenal hypoplasia congenita and are consistent with a role for DAX1 in gonadal sex determination.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenal Glands / abnormalities
  • Adrenal Glands / growth & development
  • Adrenal Glands / physiology*
  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • DAX-1 Orphan Nuclear Receptor
  • DNA, Complementary / genetics
  • DNA-Binding Proteins / genetics*
  • Disorders of Sex Development
  • Female
  • Gene Expression Regulation, Developmental
  • Humans
  • Hypogonadism / genetics
  • Hypothalamus / growth & development
  • Hypothalamus / physiology*
  • In Situ Hybridization
  • Mice
  • Molecular Sequence Data
  • Multigene Family
  • Receptors, Retinoic Acid / genetics*
  • Repressor Proteins*
  • Sequence Homology, Nucleic Acid
  • Sex Determination Analysis*
  • Species Specificity
  • Transcription Factors / genetics*
  • X Chromosome / genetics*


  • DAX-1 Orphan Nuclear Receptor
  • DNA, Complementary
  • DNA-Binding Proteins
  • NR0B1 protein, human
  • Nr0b1 protein, mouse
  • Receptors, Retinoic Acid
  • Repressor Proteins
  • Transcription Factors