EXPRESSION OF HUMAN GROUP-II PLA(2) IN TRANSGENIC MICE RESULTS IN EPIDERMAL HYPERPLASIA IN THE ABSENCE OF INFLAMMATORY INFILTRATE

Group II PLA(2) has been implicated in inflammatory processes in both man and other animals and has been shown to be involved in inflammator y conditions, such as arthritis and sepsis. Transgenic mice expressing the human group II PLA(2) gene have been generated using a 6.2-kb gen omic fragment, These mice express the group II PLA, gene abundantly in liver, lung, kidney, and skin, and have serum PLA(2) activity levels approximately eightfold higher than nontransgenic littermates. The gro up II PLA(2) transgenic mice reported here exhibit epidermal and adnex al hyperplasia, hyperkeratosis, and almost total alopecia. The chronic epidermal hyperplasia and hyperkeratosis seen in these mice is simila r to that seen in a variety of dermatopathies, including psoriasis. Ho wever, unlike what is seen with these dermatopathies, no significant i nflammatory-cell influx was observed in the skin of these animals, or in any other tissue examined. These mice provide an important tool for examining group II PLA(2) expression, and for determining the role of group II PLA(2) in normal and disease physiology. They serve as an in vivo model for identifying inhibitors of group II PLA(2) activity and gene expression.