CERVICAL VAGINAL DYSPLASIAS OF TRANSGENIC MICE HARBORING HUMAN PAPILLOMAVIRUS TYPE-16 E6-E7 GENES/

Half of the female transgenic mice harbouring human papillomavirus typ e 16 (HPV-16) E6-E7 genes under control of the mouse mammary tumour vi rus promoter, developed malignant tumours, including salivary gland ca rcinomas, lymphomas and skin histiocytomas. Although the E6-E7 genes a re aetiological factors for human anogenital carcinoma, the transgenic mice produced no tumours in the anogenital tract. We investigated cyt ological and histological changes in the anogenital tract of the same transgenic mice. Seventeen (77 %) of 22 transgenic mice developed dysp lastic and/or hyperplastic changes in the cervix and vagina. HPV-16 E6 -E7 mRNA signals were observed in the genital lesions, while they were not detected in the normal cervices and vaginas of transgenic mice an d control mice by RNA in situ hybridization analysis. RNA/PCR analysis using poly(A)(+) RNA showed that only a full-length E6-E7 RNA was exp ressed in three scraped cell samples from dysplasia, whereas full-leng th and spliced E6-E7 transcripts were in three cell samples from dyspl asia/hyperplasia. These results suggest that expression of both E6 and E7 genes of HPV-16 is important for inducing dysplastic and hyperplas tic changes in the genital epithelium.