DAX1 is an orphan member of the nuclear hormone receptor superfamily for which no ligand has yet been determined. DAX1 is important in adrenal cortical and hypothalamic development, and in sex determination: mutations in DAX1 result in adrenal hypoplasia congenital (AHC) and hypogonadotropic hypogonadism (HH), and duplication of the Xp21 genomic region that contains DAX1 results in sex reversal with XY females. DAX1 is expressed in steroidogenic tissues including hypothalamus, adrenal cortex and gonads.

This gene expression technology created by UCLA researchers provides a nucleotide sequence that drives specific expression of any gene within steroidogenic cells. As such this promoter sequence and derivatives of it may be used in gene therapy vector design where specific expression in the adrenal cortex is required. Examples would include developmental disorders of the adrenal cortex, such as AHC (requiring most commonly expression of DAX1) and congenital adrenal hyperplasia (requiring most commonly expression of 21-hydroxylase), or tumors of the adrenal cortex, such as adrenal cortical carcinoma (requiring cell-specific expression of a "suicide" gene for non-surgical adrenal cortical ablation).

UCLA researchers have demonstrated the responsiveness of the DAX1 promoter to another member of the nuclear hormone receptor superfamily, steroidogenic factor 1 (SF1), raising the possibility that gene expression by this promoter might be alterable by other molecular mediators. In addition, these researchers demonstrated expression of DAX1 in an adrenal cortical carcinoma cell line, indicating that the DAX1 promoter is a potential drug target for adrenal tumors, since we know the loss of DAX1 expression during development results in reduced size of the adrenal cortex. Due to the role of DAX1 in normal sexual development and maturation, the DAX1 promoter may be a drug target for these types of disorders as well. Availability of this isolated nucleotide sequence will permit high-throughput analysis of potential therapeutics.

Reference: UCLA Case No. 1996-507

US Patent Number: 6,465,627