Paul D. Heideman
"Model" species and our general methods
How do we use these two models? First, we brought into the laboratory a wild species of rodent (an extremely abundant field mouse, Peromyscus leucopus, the "white-footed mouse"). We found that our study population, from woods in the Williamsburg area, is naturally extremely variable in the complex brain pathway for seasonal reproduction. Then we carried out (and are still carrying out) artificial selection on the trait, and also maintained an unselected 'control' line. We created one selected line by pairing mice that only developed mature gonads in long summer day lengths. We created another selected line that developed mature gonads even in short winter day lengths. We found that a large amount of the variation in the population was indeed based on genetic differences (Heideman et al., 1999). Once we had created selected lines of mice that we knew were genetically different in this pathway, we began studying the differences between them. This system is working well for studying natural variability in this pathway. We still have to deal with the big question of correlational differences versus true cause and effect. Some physiological differences between our lines are merely correlational, while others are actually causing the different reproductive responses to photoperiod. There are two drawbacks of this white-footed mouse population as a model system. First, in comparison to laboratory rats and mice, there is much less background information and many fewer research tools available to study brain function. Second, until the Peromyscus is complete, it will remain difficult to identify genes responsible for the differences.
Our second 'model' is a set of inbred and outbred rat strains that we and other researchers have found to differ in their responses to photoperiod. Thus, these strains are either reproductively photoperiodic or reproductively nonphotoperiodic. In this case, we can compare strains to identify differences in the pathway, knowing that each individual within a strain is genetically identical. This greatly increases our chances of identifying specific differences and tracing them to specific genes. We can't do this with laboratory mice, because no one has yet been able to find a photoperiodic laboratory mouse strain, though many researchers, including some in my lab, have looked for one. There is a rat genome project in progress, and a reasonable guess is that the rat genome will be fairly well sequenced within the next few years. In addition, there are many available techniques specifically designed to study brain function in rats. There is a tremendous amount of background information already available on brain function in rats, and even on this particular photoresponsiveness pathway in rats. Finally, the domestication process has caused most strains of laboratory rats to be extremely mellow, low stress animals that are easy to study and very good-natured.
A working hypothesis in our laboratory is that the domestication and inbreeding process started with a population of rats that was variable in the photoresponsiveness pathway. If so, then some of that variation is preserved among modern rat strains, with particular genetic variants fixed in any given strain. Thus, at least some of the variability we study in rats may be sources of natural variation. We hope that we (or others) will be able to use what we discover in rats to identify the genetic basis for similar kinds of variability in natural populations of mammals.
If our strategy is a good one, and if we carry it out well, then we should be able to apply the things we learn about variation in this pathway to predict things about variation in other complex pathways. Ultimately, this will help us produce a framework to understand the role of variation in ecology, evolution, and clinical medicine.
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Last updated 3/10/2009