MOLECULAR AND FUNCTIONAL-ASPECTS OF THE HAIRLESS (HR) GENE IN LABORATORY RODENTS AND HUMANS

For many years, hairless and rhino mouse mutants have provided a usefu l and extensively exploited model for studying different aspects of sk in physiology, including skin aging, pharmacokinetic evaluation of dru g activity and cutaneous absorption, skin carcinogenesis, and skin tox icology. Interestingly, however, hairless and rhino mice have rarely b een studied for their primary cellular defect - hairlessness - and thu s, the hairless gene itself and its physiological functions have been largely overlooked for decades. The recent identification of the human homolog of the hairless gene on human Chromosome 8p12 confirmed the c linical significance of the phenomenon of ''hairlessness'' in humans, which was predicted on the basis of similarities between hairless mice and a congenital hair disorder characterized by atrichia with papules . Mutations in the hairless gene of mice provide instructive models fo r further studies of hr gene function, and may facilitate insights int o the pathophysiology of different human disorders associated with the disruption of hr gene activity. We provide an overview of current dat a on the structure and expression patterns of the hr gene, and of muta tions at the hairless locus in mice and humans, including the genetic basis of different alleles, the pathology of hairlessness, reproductiv e and immunological defects, and susceptibility to dioxin toxicity. On the basis of our current understanding of hairlessness, we speculate on the putative functions of the hr gene product in skin physiology, a nd particularly, in hair follicle biology.