Abstract
DAX1, which encodes an unusual member of the nuclear hormone-receptor superfamily, is a gene that may be responsible for a sex-reversal syndrome in humans, referred to as dosage-sensitive sex reversal, in which XY individuals carrying duplications of Xp21, part of the small arm of the X chromosome, develop as females. XY mice carrying extra copies of mouse Dax1 as a transgene show delayed testis development when the gene is expressed at high levels, but do not normally show sex reversal. Complete sex reversal occurs, however, when the transgene is tested against weak alleles of the sex-determining Y-chromosome gene Sry. These results show that DAX1 is largely, if not solely, responsible for dosage-sensitive sex reversal and provide a model for early events in mammalian sex determination, when precise levels and timing of gene expression are critical.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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DAX-1 Orphan Nuclear Receptor
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DNA-Binding Proteins / antagonists & inhibitors
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DNA-Binding Proteins / genetics
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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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Gene Dosage
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Gene Expression Regulation, Developmental*
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Humans
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Male
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Mice
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Mice, Inbred C57BL
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Mice, Inbred CBA
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Mice, Transgenic
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Nuclear Proteins*
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Ovary / embryology
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Receptors, Retinoic Acid / genetics
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Receptors, Retinoic Acid / physiology*
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Regulatory Sequences, Nucleic Acid
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Repressor Proteins*
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Sex Chromosomes
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Sex Determination Processes*
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Sex Differentiation / genetics
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Sex-Determining Region Y Protein
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Testis / embryology
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Transcription Factors / genetics
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Transcription Factors / physiology*
Substances
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DAX-1 Orphan Nuclear Receptor
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DNA-Binding Proteins
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NR0B1 protein, human
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Nr0b1 protein, mouse
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Nuclear Proteins
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Receptors, Retinoic Acid
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Repressor Proteins
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SRY protein, human
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Sex-Determining Region Y Protein
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Sry protein, mouse
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Transcription Factors