A Novel Transgenic Animal Model for HPV-Associated Cancer

Abstract

Objective: The incidence of HPV-associated tumors is rising at a rapid pace. In order to develop novel therapies with high efficacy but low toxicity, it is crucial to have an animal model in which HPV-associated oral lesions spontaneously develop. Our objective was to develop such a model.

Method: A transgene was created to target expression of E7 to the oral cavity by cloning HPV-16 E7 downstream of the L2 promoter. Transgenic mice which carry this gene were created on the C57Bl6 background. Then, these mice were backcrossed with a strain of mice heterozygous for p53.

Results: Mice were bred to create the desired genotype, E7 +/+, p53 -/-. Because of the short life span and limited breeding potential of mice with a homozygous p53 deletion, breeding was performed with p53 heterozygous mice. In accordance with Mendelian genetics, we found the majority of offspring were heterozygous for p53, and did not form spontaneous tumors. Of the offspring with homozygous p53 deletions, few lived longer than 25 weeks. However, one mouse lived long enough to develop an HPV-associated oral tumor. E7 transcript was detected in the tumor by RT-PCR, and E7 protein was detected via Western blot.

Conclusion: We report the development of a transgenic mouse which spontaneously expressed an HPV-associated oral tumor. Additional genetic manipulation may be required to enhance the longevity and stability of this mouse strain. This strain has the potential to serve as a platform to investigate novel therapeutic strategies for HPV-associated tumors.