Accelerated proliferation of epidermal keratinocytes by the transgenic expression of the platelet-activating factor receptor

Transgenic mice overexpressing platelet-activating factor receptor (PAFR) h ave abnormal pigmentation of the ear and the tail, which can progress to me lanocytic tumors as the mice age. Histologically, epidermal hyperproliferat ion and increases in dermal melanocytes are evident. Examination of these t ransgenic mice at various ages revealed hyperproliferation of the epidermis even 2 weeks after birth which developed as the mice aged. Dermal melanocy tes also increased in number with growth. Expression of the PAFR transgene was found in keratinocytes and not in melanocytes, thereby suggesting that PAF does not play a direct role in proliferation of melanocytes. Topical ap plication of a cream containing WEB2086, a specific PAFR antagonist, to the ear and the dorsal skin significantly suppressed the number of BrdU-positi ve cells in PAFR transgenic mice. These results suggest that PAF plays a mo dulatory role in the growth of epidermal keratinocytes. PAFR transgenic mic e would be a useful model for investigations of skin diseases related to al tered proliferation of epidermal keratinocytes including psoriasis.