Recapitulation of the hairless mouse phenotype using catalytic oligonucleotides: implications for permanent hair removal.
Ribozyme technology is widely used to target mRNA in a sequence-specific fashion and thus change the expression pattern of cells or tissues. While the goal of mRNA targeting is usually the cleavage of mutant mRNAs with the prospect of gene therapy for inherited diseases, in certain instances, targeting of wild-type genes can be used therapeutically. Lack of expression of the mouse hairless gene due to inherited mutations leads to the complete and irreversible loss of hair known as atrichia. We designed this study to recapitulate the hairless phenotype in a restricted manner by topical application of deoxyribozyme-targeting molecules to specifically cleave the mouse hairless mRNA. Histological samples taken from treated skin at different times demonstrated a decreased number of hair follicles, an involution of the remaining follicles, a separation of the dermal papillae, and the presence of dermal cysts, all characteristics of the hairless phenotype, but not normally present in the skin of C57Bl/6 J mice. In this study, we successfully recapitulated the hairless phenotype using topically applied target-specific catalytic oligonucleotides designed to cleave the mouse hairless mRNA. Our results demonstrate the feasibility of using ribozyme technology to alter the gene expression in the skin via topical application and provide proof of principle for the development of this strategy for permanent hair removal.
Department of Dermatology, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
Peter B
PB
Cserhalmi-Friedman
Andrey A
AA
Panteleyev
Angela M
AM
Christiano
D000818:Animals; D000831:Animals, Newborn; D015316:Genetic Therapy; D018859:Hair Follicle / Q000473:pathology; D006204:Hair Removal / Q000379:methods*; D051379:Mice; D008812:Mice, Hairless; D008810:Mice, Inbred C57BL; D010641:Phenotype; D016337:RNA, Catalytic; D012333:RNA, Messenger / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics*
D016337:RNA, Catalytic; D012333:RNA, Messenger; D014157:Transcription Factors; C088661:hr protein, mouse