Animal model system for photodamage, photoaging and skin wounding
Non-human mammalian animals having a higher epidermal expression level of protein kinase Cε than their wild-type counterparts are phenotypically distinguished from wild-type animals in that the animals induced to develop tumors in a chemical initiation/promotion protocol are suppressed for subsequent papilloma development but are susceptible to developing squamous cell carcinoma and metastatic squamous cell carcinoma. The animals are advantageously used in methods for screening putative agents for altering the susceptibility, development and progression of squamous cell carcinoma and metastatic squamous cell carcinoma and have further commercial value as tools for investigating the development of metastatic disease.
1. A method for identifying an agent for reducing or preventing an effect of UV radiation on skin of a human or non-human animal, the method comprising the steps of:
exposing a genetically modified FVB/N mouse having epidermal cells that comprise a protein kinase Cε activity higher than that of wild-type FVB/N epidermal cells to an amount of UVB radiation sufficient to induce an effect selected from the group consisting of photodamage, photoaging, and skin wounding;
administering to the mouse at least one agent; and
determining whether the at least one agent can reduce or prevent photodamage, photoaging or skin wounding.
2. A method as claimed in claim 1 wherein the mouse has epidermal cells that comprise a protein kinase Cε activity at least twelve times higher than that of wild-type FVB/N epidermal cells.
3. A method as claimed in claim 1 wherein the mouse has epidermal cells that comprise a protein kinase Cε activity at least fifteen times higher than that of wild-type FVB/N epidermal cells.
4. A method as claimed in claim 1 wherein the mouse has epidermal cells that comprise a protein kinase Cε activity at least eighteen times higher than that of wild-type FVB/N epidermal cells.
5. A method as claimed in claim 1 wherein the amount of UV radiation is in the range from about 1 to 10 kj/m 2 .
6. A method as claimed in claim 1 wherein the amount of UV radiation is in the range from about 4 to 10 kj/m 2 .
7. A method as claimed in claim 1 wherein the amount of UV radiation is in the range from about 6 to 8 kj/m 2 .