The Hole Story:
The Mouse Model of Cancer ctd.
The Tanning Mouse
The laboratory actually has several strains of hairless mice. The albino mice form the basis for most of the experiments. They don't tan because they don't have any pigment in their skin. But there is a pigmented strain of hairless mice unique to this laboratory and developed there from the original strain of hairless mice that were obtained from a laboratory in Philadelphia. This particular strain of mice has the capacity to tan so it is used for measuring the protective effect of a suntan and also the capacity of topical substances to stimulate a tan. It is being used to see what sort of long term effect a suntan has on the development of skin cancer.
This tanning mouse is a very useful little mouse. It was bred up from the hairless pigmented mice almost by accident. We weren't aiming for a tanning mouse, says Reeve. When we first saw different coloured pups in the litters we thought how cute. It all started from how cute, aren't they sweet, and it was later on that we discovered that when we were exposing them to UV light, some of them produced wonderful tans whereas the others didn't tan. So we looked back into the genetics and then tried to only breed mice that would tan and eventually ended up with a line of mice that had this tanning capacity, which we identified by their black juvenile coats.
These mice actually grow a hair coat when they are tiny, their first hair coat. Then when the hair would normally go into the resting phase of the hair cycle this hair all breaks off, falls out and these mice never grow a second coat. She managed to separate out three different pigmentation characteristics and then bred them up separately into pure lines; a grey mouse, a black mouse and a beige mouse. The colour of the coat is the only indication about the genetic origins of its basic pigment colour.
The black mouse is the one that's capable of tanning because the pigment is in the epidermis, in the upper layer of the skin, which is quite unique and different from other strains of mice. The tanning mechanism in these mice is similar to humans, and can be checked by looking at sections of mouse skin under the microscope. It is possible to actually see the pigment granules located in the epidermis, where as most mice produce pigment only in the deeper parts of the skin.
Research is being carried out to find a way to induce melanoma in the tanning mouse. Because of the complexity of melanoma cancer, as opposed to other types of skin cancer, it is important to look in different ways at the relationship of the mutation, UV light and melanoma. One approach being contemplated is that instead of just using UV light they could use the total sunlight spectrum which may be found to have some effect on the induction of melanoma.
The big problem with melanoma is that it often appears on parts of the body that have not been exposed to UV radiation. This is in contrast to the other types of skin cancers which almost always appear on the sun exposed sides. So the relation between the high incidence of melanoma and sunlight is less direct. It also has a different pattern of expression. Whereas the non-melanoma skin cancers seem to take a long time to develop in humans, between 30 and 40 years, the melanoma skin cancers may appear in early life. They don't follow the same pattern as other skin cancers. But it does seem that things like early exposure, especially high childhood exposure, like specific sunburn doses, may influence the development of melanoma. If this complexity can be unravelled in animal models it will be of direct benefit to our understanding of melanoma and its relationship to UV exposure.
At the moment we simply don't know, says Gavin Greenoak. Once melanomas can be routinely induced in mice it will then be possible to dissect their induction and find out what essential steps are necessary to reduce and prevent them. Perhaps melanomas will turn out to require a specific wavelength of light to be started or other cancer agents might be involved. But this can't be done without an animal model. At present all that the researchers have to work on is already induced melanoma cell lines in culture and human patients appearing with the disease, upon whom research is limited.