Modulation of murine hair follicle function by alternations in ornithine decarboxylase activity

Mice that overexpress a mutated ornithine decarboxylase (ODC) transgene in outer root sheath keratinocytes of the hair follicle were used to study the role of this enzyme in regulating hair follicle structure and function. These transgenic mice have a normal first hair cycle, but lose their hair completely beginning 2-3 wk after birth. Transgene overexpression in follicular keratinocytes is first detected at day 12 after birth, coincident with the development of follicular cysts in the upper portion of the dermis. The onset of keratin 6 expression also begins around day 12; because the promoter/regulatory region of the bovine keratin 6 gene was used to target ODC transgene expression to hair follicle keratinocytes, these data demonstrate the faithful temporal and cell type-specific expression of the K6-driven transgene. The ODC inhibitor 2-difluoromethylornithine could prevent hair loss and partially normalize skin histology if administered before the onset of ODC overexpression. 2-Difluoromethylornithine could also reactivate hair growth in animals with complete hair loss. Our results suggest that ODC is an important regulatory gene for the mouse hair follicle.