TRANSGENIC MICE FOR THE E5 ONCOGENE OF HUMAN PAPILLOMAVIRUS TYPE-18

A subset of Human Papillomaviruses (HPV) is associated with more than 90% of cervical carcinomas. The principal transforming genes of the ca ncer-associated HPVs (type 16 and 18) are E6 and E7 although recent st udies point out the transforming role of E5 gene. In order to investig ate the action of this gene in differentiating epithelia, transgenic m ice containing E5 gene of HPV type 18 - that clinical data indicate mo re aggressive than type 16 - have been produced. We have inserted the HPV18 E5 sequence into the vector pEV142 than contains the mouse metal lothionein (MT-1) heavy metal inducible promoter fused to polyadenilat ion signal sequence of the human growth hormone gene. By transgene mic roinjection into the mouse fertilised eggs ten founders were obtained. The mice with the highest transgene copy number have been chosen to e stablish the lineages and, at present, four families are under observa tion. The transgene is transcriptionally active as demonstrated by the presence of specific E5 transcripts in the liver extracts of members of one of these families. Some phenotypic changes have been detected a nd linked to the presence of the MT-ES transgene. These data indicate that the model will be useful to study the interactions between HPV18 E5 oncoprotein and cellular factors.