CHARACTERIZATION OF MOUSE AND HUMAN NUDE GENES

The differentiation of primitive epithelial precursor cells in the thy mic primordium into subcapsular, cortical, and medullary epithelial ce lls of the mature thymus requires the activity of the nude gene produc t Whn. Whn is also required for proper keratinization of the hair shaf t. We determined the nucleotide sequence of a 58 kilobase region on mo use chromosome 11 that encompasses the mouse nude gene and part of the two neighboring genes, encoding a sodium/dicarboxylate co-transporter and the retinal protein 4. Using cross-hybridization, the human ortho logue of the mouse nude gene was isolated. The human WHN protein also consists of 648 amino acids, 85% of which are identical to the mouse p rotein. Like the mouse gene, the human gene consists of eight coding e xons and utilizes two alternative first exons in a tissue-specific fas hion. Sequences upstream of the two alternative first exons display pr omoter activity in heterologous reporter assays. Whereas both promoter s appear to be active in skin (albeit at different levels), only the m ost upstream element is active in the thymus, indicating that transcri ptional activity of the whn gene is subject to complex regulation. Nuc leotide sequence database comparisons reveal that among other winged-h elix genes, the HTLF and HTLFL1 genes are most closely related to whn, although the exon/intron structure of the human HTLF gene in the DNA binding domain differs from that of whn.