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Modulation of murine hair follicle function by alterations in ornithine decarboxylase activity
A P Soler1, G Gilliard, L C Megosh
1Lankenau Medical Research Center, Wynnewood, Pennsylvania 19096, USA.
Abstract:
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 of 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.
Insights
Overexpression of mutated ornithine decarboxylase (ODC) in mouse hair follicles causes hair loss. Inhibiting ODC with 2-difluoromethylornithine prevents hair loss and promotes regrowth, highlighting ODC
Area of Science:
- Dermatology
- Molecular Biology
- Genetics
Background:
- The role of ornithine decarboxylase (ODC) in hair follicle structure and function is not fully understood.
- ODC is a key enzyme in polyamine synthesis, which is crucial for cell growth and differentiation.
Purpose of the Study:
- To investigate the function of ornithine decarboxylase (ODC) in regulating hair follicle morphogenesis and cycling.
- To determine the effects of ODC overexpression and inhibition on hair follicle development and hair loss.
Main Methods:
- Generation of transgenic mice overexpressing a mutated ornithine decarboxylase (ODC) transgene in outer root sheath keratinocytes.
- Utilized a bovine keratin 6 (K6) gene promoter to achieve cell type-specific and temporal expression of the ODC transgene.
- Administered the ODC inhibitor 2-difluoromethylornithine to assess its effects on hair loss and skin histology.
Main Results:
- Transgenic mice exhibited normal first hair cycles but developed complete hair loss starting 2-3 weeks after birth.
- ODC transgene overexpression and onset of keratin 6 expression were detected around day 12 post-birth, coinciding with follicular cyst development.
- 2-difluoromethylornithine administration prevented hair loss, partially normalized skin histology, and reactivated hair growth in affected mice.
Conclusions:
- Ornithine decarboxylase (ODC) plays a critical regulatory role in mouse hair follicle development and maintenance.
- Targeting ODC activity presents a potential therapeutic strategy for managing hair loss conditions.