Preclinical Changes in Weight of Scrapie-lnfected Mice as a Function of Scrapie Agent-Mouse Strain Combination

Abstract

Several inbred strains of mice were injected with different scrapie agents and their total body weight was monitored throughout the incubation period. As a control, mice were injected with normal mouse brain homogenate. For most combinations of scrapie agent and mouse strain, weights during the preclinical phase were similar to or lower than the average weight of controls. For some combinations there was a significant increase in weight (compared to controls) during the latter part of the preclinical phase of disease. The effect was dependent on both agent and mouse strain, i. e., in some cases a mouse strain showed the increase with one scrapie agent but not another and some scrapie agents caused the increase in one inbred strain of mouse but not in another strain. The increase in weight was due to accumulations of fat rather than a generalized increase in weight of various organs. With one mouse strain (SJL), there was increased vacuolation seen in the hypothalamus of mice injected with scrapie agents that showed the increase in weight compared to the lesion intensity with an agent which did not cause the weight increase.

Variation in the characteristics of 10 mouse-passaged scrapie lines derived from five scrapie-positive sheep

“…A second parameter analysed was the capacity of the isolate lines to induce a weight increase during the preclinical phase of disease. In some scrapie strainmouse strain combinations there is an increase in body weight prior to the appearance of typical signs of clinical scrapie (Outram, 1972;Carp et al, 1984Carp et al, , 1989cKim et al, 1987b). In a series of studies, it was established that the mouse strain, sCrapie strain and route of injection all play a role in the occurrence of a significant increase in weight (Kim et al, 1987b).…”

“…The importance of scrapie strain can be seen by the fact that in the same mouse strain (SJL) using the same route of injection (i.c. ), two scrapie strains caused a significant weight increase whereas two other scrapie strains did not (Carp et al, 1984). It was of interest to examine the sheep isolates for their capacity to induce a weight increase.…”

“…Clinical symptoms were monitored and incubation periods estimated as described previously (Carp et al, 1984). Incubation periods are expressed as mean + S.E.…”

“…Body weight was monitored periodically throughout the incubation period as described previously (Carp et al, 1984(Carp et al, , 1989c. Comparisons of mean weight values were performed using Student's t-test.…”

“…Passages from a single host into different species (Kimberlin & Walker, 1977, 1978Kimberlin et al, 1987Kimberlin et al, , 1989, or into mice with different Sinc genotypes (Dickinson & Outram, 1983), often yield scrapie agent populations with different characteristics. The passage lines were analysed for two parameters that are under genetic control of host and agent: incubation periods in mice of different Sinc genotypes (Dickinson & Meikle, 1971) and increase in weight during the preclinical phase of disease (Outram, 1972;Carp et al, 1984Carp et al, , 1989cKim et al, 1987 b). In the present study, initiation of lines from the same sheep in different Sinc genotypes led to differences in one or both parameters.…”