Use of a human skin-grafted nude mouse model for the evaluation of topical retinoic acid treatment.
Cultured human keratinocytes and artificial dermal equivalents maintained in vitro do not perfectly mimic the terminal differentiation patterns and response to drugs observed in intact human skin. We have made use of human skin grafted onto nude mice to demonstrate that such grafts maintain the pattern of pharmacologic responsiveness to all-trans retinoic acid previously reported in human subjects. The use of a quantitative polymerase chain reaction method to measure induction of a retinoic acid responsive gene, cytoplasmic retinoic acid binding protein II, has made it possible to generate objective data suitable for investigations of drug efficacy. This method of using grafted human skin has potential broad applicability for investigation of topical drugs in a number of therapeutic fields.
Otulakowski
G
G
R. W. Johnson Pharmaceutical Research Institute, Don Mills, Ontario, Canada.
Zhou
L
L
Fung-Leung
W P
WP
Gendimenico
G J
GJ
Samuel
S E
SE
Lau
C Y
CY
D000287:Administration, Topical; D000818:Animals; D001483:Base Sequence; D001706:Biopsy; D005260:Female; D006652:Histological Techniques; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude / Q000502:physiology*; D008954:Models, Biological; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D012867:Skin / Q000033:anatomy & histology / Q000187:drug effects; D016038:Skin Transplantation / Q000502:physiology*; D014212:Tretinoin / Q000008:administration & dosage* / Q000627:therapeutic use
D014212:Tretinoin