OVEREXPRESSED MAX IS NOT ONCOGENIC AND ATTENUATES MYC-INDUCED LYMPHOPROLIFERATION AND LYMPHOMAGENESIS IN TRANSGENIC MICE

The cellular growth promoting function of the Myc oncoprotein requires its heterodimerization with the Max protein, but Max can also form co mplexes that inhibit Myc action. To determine whether man overexpressi on in vivo is oncogenic and whether it can modulate the action of Myc, we generated transgenic mice in which the max gene was directed to ex press in lymphoid cells by a linked immunoglobulin heavy chain enhance r (E mu). Expression of the transgene at substantially higher levels t han the endogenous max gene did not perturb lymphoid homeostasis in ad ult animals nor predispose to lymphomagenesis. The numbers of B-lympho id cells in very young animals were reduced. Moreover, analysis of bi- transgenic E mu-myc/E mu-max mice revealed that man overexpression att enuated the premalignant B-lymphoproliferative state induced by an Ep- myr: transgene and reduced the rate of lymphoma onset. These results s uggest that elevation of Max expression in vivo inhibits the function of Myc.