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JOURNAL ARTICLE
REVIEW
DAX1: Increasing complexity in the roles of this novel nuclear receptor.
Molecular and Cellular Endocrinology 2007 Februrary
DAX1 (NR0B1) is a nuclear receptor with a characteristic C-terminal ligand binding domain, but an atypical DNA binding domain. Mutations in the DAX1 gene cause adrenal hypoplasia congenita (AHC) establishing its biological importance. Recent studies highlight the complexities of DAX1 regulation and function. There is considerable phenotypic variability in AHC suggesting the existence of DAX1 modifier genes and environmental influences on DAX1 function. The findings of an alternatively spliced DAX1A, more common than DAX1 in all tissues except testis, of DAX1 homodimers, and of DAX1 heterodimers with a number of transcription factor partners including DAX1A and SHP point to an expanded transcription regulatory network under DAX1 control. Model organisms (mice and zebrafish) are being used to identify other DAX1 functions and modifier genes to understand the pathogenesis of AHC and the lack of genotype-phenotype correlation.
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