Generation of two distinct functional isoforms of dosage-sensitive sex reversal-adrenal hypoplasia congenita-critical region on the X chromosome gene 1 (DAX-1) by alternative splicing.

DAX-1 (dosage-sensitive sex reversal-adrenal hypoplasia congenita-critical region on the X chromosome gene 1; NR0B1) is an orphan nuclear receptor that plays an important role in the development and functioning of the adrenal gland and hypothalamic-pituitary gonadal axis. The DAX-1 protein acts as a transcriptional repressor of genes involved in the steroidogenic pathway. We have identified a novel isoform encoded by the known exon 1 of DAX-1 and a previously unrecognized exon (exon 2alpha) that lies within intron 1 of DAX-1. This novel transcript, which we designated DAX-1alpha, is terminated at exon 2alpha; the last 70 amino acids of the C-terminal repressor domain encoded by exon 2 are absent. DAX-1alpha encodes a protein of 401 amino acids; the first 389 amino acids are encoded by exon 1 and the last 12 are encoded by exon 2alpha. Using conventional RT-PCR and real-time RT-PCR analyses, we found that DAX-1alpha is abundantly expressed in the adrenal gland, brain, kidney, ovary, and testis. We also found that DAX-1alpha can bind to steroidogenic factor 1 and to DNA but is unable to repress steroidogenic factor 1-mediated transcriptional activation of the reporter gene and acts as an antagonist of DAX-1 under certain conditions.