NEW MEMBER OF THE WINGED-HELIX PROTEIN FAMILY DISRUPTED IN MOUSE AND RAT NUDE MUTATIONS

MUTATIONS at the nude locus of mice and rats disrupt normal hair growth and thymus development(1,2), causing nude mice and rats to be immune-deficient. The mouse nude locus has been localized on chromosome 11 (refs 3, 4) within a region of <1 megabase(5). Here we show that one of the genes from this critical region, designated whn, encodes a new member of the winged-helix domain family of transcription factors(6.7), and that it is disrupted on mouse au and rat rnuN alleles. Mutant transcripts do not encode the characteristic DNA-binding domain, strongly suggesting that the whn gene is the nude gene. Mutations in winged-helix domain genes cause homeotic transformations in Drosophila(8) and distort cell-fate decisions during vulval development in Caenorhabditis elegans(9). The whn gene is thus the first member of this class of genes to be implicated in a specific developmental defect in vertebrates.