UCSF researchers have generated and validated a K14-HPV16 transgenic mouse model, in which transgene expression produces neoplastic progression that fully resembles the gynecological and other epithelial dysplastic lesions induced by high risk HPVs. This model offers an invaluable tool for studying HPV infection and developing new drugs for HPV treatment.
Human papillomavirus (HPV) is the most widespread sexually transmitted infection. Nearly all men and women who are sexually active get infected at some point in their lives. The most dangerous health threat from HPV is the association of anogenital cancers with infection by specific high risk HPVs including viral types 16,18, 33, 35. These HPV types can be detected in 90% of anogenital malignancies. HPV infection starts from the basal keratinocytes of the cervical squamous mucosa in women. It produces increased number of keratinocytes and forms hyperplastic lesions. With accumulation of immature cells, it turns into high-grade dysplasia and eventually causes cancer. There were no transgenic models of the cervico-vaginal neoplastic progression before the k14-HPV16 mice were developed. By targeting HPV16 expression to the critical keratinocytes and altering the sex hormone balance in the reproductive tracts, these k14-HPV16 mice fully resemble the neoplastic progression from hyperplasic lesions to higher grades of dysplasia.The current invention provides the following advantages:
Through expression of HPV16 early region under the control of a 2kb keratin-14 (K14) promoter/enhancer region, the inventors at UCSF have developed a mouse model that recapitulates the progressive dysplasia in various tissues of HPV16 infected patients. With exogenous estrogen treatment, these transgenic mice express the oncogenes of HPV16 in the basal cells of a variety of squamous epithelia including vagina, cervix, skin, oral cavity and anus. Most importantly, this animal model can induce the precise pathology of high risk HPV infection in humans, especially the progression of cervico-vaginal squamous dysplasia.
To use the mouse model as a tool to investigate drugs and treatments that would prevent the development of HPV-induced dysplasia and cancers.
Animal data available
|United States Of America||Issued Patent||5,709,844||01/20/1998||1994-B56|
K14-HPV16, Mouse model, HPV infection, Cervico-vaginal dysplasia, Epithelial neoplasia, Drug discovery, Immune-therapy