The differentiation of repeated epilation (Er/Er) mouse mutant skin in organ culture and in grafts.

The homozygous repeated epilation (Er/Er) mouse mutant dies at birth and shows a variety of malformations, one of which is a skin defect. The developmental abilities of skin fragments from these Er/Er mouse embryos were studied in organ culture and in grafts performed either under the renal capsule of young mouse hosts or under the skin of mouse fetuses. In organ culture, the skin fragments differentiated in accordance with their genetic origin. The most characteristic feature was the abnormally thickened spinous layer and the formation of numerous epidermal nodules in Er/Er skin pieces removed from 13- to 16-day-old embryos, and cultured for 4 to 6 days, whereas the normal skin showed a constant layered organization. As in normal skin, keratin fibers developed within 4 to 6 days of culture. However, in contrast to normal skin, where keratin sheaths developed all over the surface of the epidermis, the Er/Er skin exhibited keratin masses inside the nodules. Combinations of mutant Er/Er epidermis with normal dermis resulted in abnormal skin differentiation, with formation of nodules similar to those observed for unseparated Er/Er skin fragments, whereas the reciprocal combination (normal epidermis with Er/Er dermis) produced normal skin differentiation. Cornified layers developed in both types of explants. Grafts of Er/Er and, for comparison, of normal skin fragments under the renal capsule or under a fetus's skin showed that the development of Er/Er skin in a normal or Er/+ host was similar to that of a normal skin. Thus, if isolated from the mutant organism, and inserted into a normal environment, the skin recovered within 6 to 7 days after transplantation and then developed normally. Our experiments suggest that the abnormal skin development of the Er/Er mutant might be caused by environmental influences.