Abstract
The DAX-1 gene has been involved in the dosage sensitive sex reversal (DSS) phenotype, a male-to-female sex-reversal syndrome due to the duplication of a small region of human chromosome Xp21. Dax-1 and Sry have been shown to act antagonistically in the mouse system, where increasing expression of the former leads to female development and increasing activity of the latter to male development. Although these data strongly implicate DAX-1 in sex determination, the mouse and human proteins appear to behave differently. Absence of DAX-1 is responsible for adrenal hypoplasia congenita, a human inherited disorder characterized by adrenal insufficiency and hypogonadotropic hypogonadism. Unlike human patients, Dax-1-deficient XY mice have normal levels of corticotropins and adrenal hormones but are sterile. Dax-1-deficient females are fertile. The DAX-1 protein, an unusual member of the nuclear hormone receptor, may act as a transcriptional repressor. It has been shown to both repress transcriptional activators by direct protein-protein interactions and to bind DNA hairpin structures and repress target genes.
MeSH terms
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Adrenal Glands / embryology
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Adrenal Insufficiency / congenital
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Adrenal Insufficiency / genetics
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Animals
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DAX-1 Orphan Nuclear Receptor
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DNA-Binding Proteins / genetics*
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DNA-Binding Proteins / metabolism
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DNA-Binding Proteins / physiology
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Disorders of Sex Development
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Female
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Fushi Tarazu Transcription Factors
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Gene Dosage
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Gene Duplication
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Gene Expression Regulation, Developmental
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Homeodomain Proteins
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Humans
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Male
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Mice
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Mice, Transgenic
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Phosphoproteins / genetics
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Phosphoproteins / physiology
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Promoter Regions, Genetic
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Receptors, Cytoplasmic and Nuclear
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Receptors, Retinoic Acid / genetics*
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Receptors, Retinoic Acid / metabolism
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Receptors, Retinoic Acid / physiology
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Recombinant Fusion Proteins / physiology
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Repressor Proteins*
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Sequence Deletion
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Sex Determination Processes*
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Sex Differentiation / genetics*
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Species Specificity
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Steroidogenic Factor 1
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Transcription Factors / genetics*
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Transcription Factors / metabolism
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Transcription Factors / physiology
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Transcription, Genetic
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X Chromosome / genetics
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Y Chromosome / genetics
Substances
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DAX-1 Orphan Nuclear Receptor
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DNA-Binding Proteins
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Fushi Tarazu Transcription Factors
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Homeodomain Proteins
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NR0B1 protein, human
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Nr0b1 protein, mouse
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Phosphoproteins
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Receptors, Cytoplasmic and Nuclear
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Receptors, Retinoic Acid
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Recombinant Fusion Proteins
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Repressor Proteins
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Steroidogenic Factor 1
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Transcription Factors
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steroidogenic acute regulatory protein