116 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS was completely unexpected. We tend to regard muco-cutaneous junc- tions, such as the vermilion border of the lip, and that presenting between the skin and conjunctiva in the eyelid, as fixed and immutable anatomical landmarks. Think how disastrous it would be for us if, as a result of some change in hormonal or vitamin status, epidermal epithelium was able to transgress these natural and biologically important frontiers, re- placing the native type of epithelium with one having entirely different structural and physiological properties. The normal, dermal-epidermal interaction systems so far described have been those producing variant forms of superficial epidermis. Other local forms of this kind of interaction must underlie the morphogenic activity of the germinal cells in epidermal appendages such as hairs and nails. These, too, require special techniques, including grafting, for their analysis. Studies by Cohen (13) and Oliver (14) on the transplanta- tion of follicle components, most conveniently those of vibrissae in rats, have been especially informative. ANALYSIS OF A GENETIC DEFECT IN MOUSE SKIN The procedures described above to study how the specificities of the various epidermal differentia are maintained can also be employed to analyze congenital and other abnormalities affecting' the skin. In the mouse there is a genetically determined form of baldness of early onset (15). The infants develop a normal fur crop but this begins to shed from about the 10th day postpartum. After a few hair growth cycles affected animals become completely bald. The fact that their toenails are long and that adult bald females seem to be incapable of nursing their infants properly hints that the genetic lesion, which is caused by an autosomal recessive gene, hr, affects the entire cutaneous system, including mam- mary glands. This abnormality has been under study by the author in collaboration with Drs. Shaffer and Mann (16). To determine whether the defective hr gene acts systemically, for example by affecting the availability of some metabolite essential for the growth of the hair, or whether it acts locally within the integument required simple grafting experiments (17). It was found that skin from normal mice consistently produces and main- tains a crop o[ normal fur of donor type when transplanted to bald hosts, whereas skin from bald donors conserves its abnormal status when caused to grow on normal mice. Furthermore, when skin grafts are removed from hr/hr fetuses that are destined to shed their fur if allowed to be born and grow up, and are transplanted to normal mice, they develop

TRANSPLANTATION OF SKIN 117 fur at first but then become bald. Evidently, the defective gene exerts its influence within the skin. To determine whether the site of action of the mutant gene is within the epidermis or the dermis required the production of heterotypic re- combinant grafts. With the aid of collagenase, skin from neonatal mice of normal and abnormal genotypes was separated into its epidermal and dermal components and recombinant grafts were transplanted to ge- netically normal hosts. It was found that when epidermis from puta- tively abnormal skin was combined with phenotypically normal dermis, a permanent fur crop developed. The converse experiment, entailing recombination of normal epidermis with the dermis from mutant new- born mice, is in progress. Subject to confirmation by the results of this latter experiment, the present findings indicate that the genetic defect operates at the level of the derreal components of the hair follicles. One important prerequisite fo.r the experimental approach outlined above is that the grafts had to be accepted by their hosts for long periods. In most cases titis was ensured by the use of appropriate inbred strains of mice and their F• hybrid progeny. In some instances in which it was necessary to tra•splant skin grafts to genetically incompatible hosts, the latter were tree, ted with rabbit antimouse lymphocyte serum (ALS) to suppress the homograft rejection reaction that would otherwise have been incited (18). The approach outlined above should be applicable to elucidate cer- tain enigmatic skin lesions in man, genetically determined or otherwise. Lance and Mcdawar (19) have shown that treatment of mice with ALS enables them •o accept heterografts of human skin for many weeks. It should thereft•re be possible to prepare dermo-epidermal recombinant grafts using skin components from normal persons and from persons af- fected by such conditions as ichthyoses and psoriasis and maintain them on murine hosts to determine whether the abnormalities are at the level of the dermis c, r the epidermis. (Received August 5, 1970) REFERENCES (1) Billingham, R. E., and Silvers, W. K., Some Unsolved Problem, in the Biology of Skin, in Lyne, A. G., and Short, B. F., Biology of the Shin and Hair Growth, Angus and Robertson, Sydney, 1965, pp. 1-24. (2) Billingham, R. E., and Silvers, W. K., Studies on the conservation of epidermal specifici- ties of skin and certain mucosas in adult matnmals, J. Exp. Med., 125, 429-46 (1967). (3) Grobstein, C., Mechanisms of Organogenetic Tissue Interaction, Nat. Cancer Inst., Monogr. No. 26, 279-99 (1967).