USE OF A HUMAN SKIN-GRAFTED NUDE-MOUSE MODEL FOR THE EVALUATION OF TOPICAL RETINOIC ACID TREATMENT

Cultured human keratinocytes and artificial dermal equivalents maintai ned in vitro do not perfectly mimic the terminal differentiation patte rns and response to drugs observed in intact human skin. We have made use of human skin grafted onto nude mice to demonstrate that such graf ts maintain the pattern of pharmacologic responsiveness to all-trans r etinoic acid previously reported in human subjects. The use of a quant itative polymerase chain reaction method to measure induction of a ret inoic acid responsive gene, cytoplasmic retinoic acid binding protein II, has made it possible to generate objective data suitable for inves tigations of drug efficacy. This method of using grafted human skin ha s potential broad applicability for investigation of topical drugs in a number of therapeutic fields.