It is proposed that the difference between animals resistant and susceptible to the African trypanosomes is primarily due to differences in their innate ability to control parasitemia, and to more rapidly induce the long-slender (LS) to short stumpy (SS) transition. Hosts that induce an early change to the SS stage are better able to mount an immune response, and therefore to survive longer. In addition, it is further suggested that different clones of the trypanosomes vary in their sensitivity to the factor(s) inducing this morphological change, and therefore their rate of transformation. It is hypothesized that the rate of change of individual clones is directly correlated with differences in virulence between clones.
The specific aims are: 1. To verify the hypothesis that different animals differ genetically in their ability to control parasitemia, and the rate at which they induce the morphological change. First, additional immunosuppressed inbred mouse lines will be examined for these characteristics, and then through classical genetic studies involving crosses and backcrosses to define the genetics of these traits. For example, is there one or multiple genes controlling the rate of morphological transition and parasitemia? Is the resistant phenotype (ability to control parasitemia) a dominant or recessive trait? 2. To further explore the suggestion that the parasite genotype is important in determining the rate of morphological transition from the LS to the SS form and to demonstrate that different trypanosome clones vary in their sensitivity to the environmental triggers which induce these changes. 3. To begin to explore the mechanism of resistance by determining the physiological factor(s) involved in the host control of parasitemia, and the rate of morphogenesis.
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