919 Overexpression of cyclooxygenase-2 in the skin of adult transgenic mice leads to sebaceous gland hyperplasia and thinning of hair shafts

Abstract

Current methods of modeling androgenetic alopecia (AGA), or male pattern baldness as it is more commonly known, in mice have used the constitutive expression of cyclooxygenase-2 (COX-2), an enzyme involved in the synthesis of prostaglandin D2 (PGD2), which is known to inhibit hair growth. However, this model cannot determine the effect of induced COX-2 expression in adult mice, which is of particular importance given that pathogenesis of AGA presents in mature hair follicles, nor can it determine whether a normal hair phenotype can subsequently be recovered after reducing COX-2 expression. To answer this, we generated transgenic mice expressing K5-rtTA and TRE-COX2, allowing for the doxycycline (dox) induced expression of COX-2 targeted to the skin. Adult (>2 months old) transgenic mice on dox for a period of 2.5 months showed a significant increase in sebaceous gland crosssectional area (p¼0.0032) and a significant decrease in the diameter of guard/awl (p¼0.025), auchene (p¼0.009), and zigzag (p¼0.008) hairs compared to control mice. Dox was then removed from a subset of transgenic mice for 2.5 months during which the hair follicles progressed through anagen resulting in the recovery of control level hair diameter (guard/awl p¼0.15; auchene p¼0.3; zigzag p¼0.07) while the hair diameter of mice left on dox remained significantly smaller (guard/awl p¼0.002; auchene p¼0.019; zigzag p¼0.01). Sebaceous gland area remained significantly increased for both the mice taken off dox (p¼0.0042) and left on dox (p¼1.3e-5). These results indicate that this model can phenocopy the hair follicle miniaturization and sebaceous gland enlargement characteristics of human AGA in adult mice and suggest that targeting the PGD2 pathway may lead to reversal of these symptoms.