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 cancer-associated HPVs (type 16 and 18) are E6 and E7 although recent studies point out the transforming role of E5 gene. In order to investigate the action of this gene in differentiating epithelia, transgenic mice containing E5 gene of HPV type 18 - that clinical data indicate more aggressive than type 16 - have been produced. We have inserted the HPV18 E5 sequence into the vector pEV142 than contains the mouse metallothionein (MT-1) heavy metal inducible promoter fused to polyadenylation signal sequence of the human growth hormone gene. By transgene microinjection into the mouse fertilised eggs ten founders were obtained. The mice with the highest transgene copy number have been chosen to establish the lineages and, at present, four families are under observation. 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 and linked to the presence of the MT-E5 transgene. These data indicate that the model will be useful to study the interactions between HPV18 E5 oncoprotein and cellular factors.