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Genetic control of scrapie: incubation period and plaque formation in I mice
Abstract:
The host component of control of scrapie incubation period in the mouse is manifested largely through the action of the Sinc gene. Only one mouse strain (VM) has been found that is p7p7 (prolonged incubation for ME7 agent) and two other strains have been derived from VM. All other strains, designated s7s7, have a short incubation for ME7. In the present study, the I strain was shown to fulfil the criteria that are characteristic of mouse strains with the p7 allele of Sinc: a comparatively long incubation period for ME7 and a short incubation period for 22A, the incubation period for F1 hybrid mice (s7s7 X p7p7) either fell between the incubation periods for the parental strains (with ME7) or were longer than either parent (with 139A and 22A), amyloid plaques occurred following injection of ME7 and 87V but not after 22A or 139A, lesion profiles for four scrapie strains were similar in I mice and p7p7 mouse strains, and injection of 87V led to disease in less than 300 days. Finally, allelism tests using F1 hybrid mice (I X a p7p7 mouse strain) and progeny of backcrosses between these F1 mice and I mice failed to reveal the segregation of additional major genes affecting scrapie incubation period.
Insights
The Sinc gene influences scrapie incubation periods in mice. The I mouse strain exhibits characteristics of the p7 allele, suggesting it does not segregate additional major genes affecting incubation time.
Area of Science:
- Neuroscience
- Genetics
- Veterinary Medicine
Background:
- The incubation period of scrapie, a prion disease, is significantly influenced by host genetics, primarily the Sinc gene in mice.
- Specific alleles of the Sinc gene (p7 and s7) are associated with distinct incubation periods when challenged with different scrapie strains.
Purpose of the Study:
- To characterize the I mouse strain in relation to the Sinc gene and its control of scrapie incubation periods.
- To determine if the I strain possesses the p7 allele of the Sinc gene and investigate the presence of other major genes affecting incubation time.
Main Methods:
- Phenotypic analysis of scrapie incubation periods in I mice, F1 hybrids, and backcross progeny following inoculation with various scrapie strains (ME7, 22A, 139A, 87V).
- Histopathological examination for amyloid plaque formation and lesion profiling in the brains of infected mice.
- Allelism tests using F1 hybrid and backcross generations to assess gene segregation.
Main Results:
- The I mouse strain exhibited a prolonged incubation period with the ME7 agent and a short incubation period with the 22A agent, consistent with the p7 allele.
- Amyloid plaques were observed with ME7 and 87V, but not 22A or 139A. Lesion profiles were similar to known p7p7 strains.
- F1 hybrid mice showed intermediate or prolonged incubation periods, and allelism tests did not reveal segregation of additional major genes influencing scrapie incubation.
Conclusions:
- The I mouse strain possesses the p7 allele of the Sinc gene.
- No additional major genes influencing scrapie incubation period were identified in the I mouse strain.
- This finding contributes to understanding the genetic control of prion disease pathogenesis.