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Scrapie incubation periods and end-point titers in mouse strains differing at the H-2D locus
Abstract:
In extending findings on the influence of the mouse H-2D locus on the scrapie incubation period, we showed that with the intracerebral (i.c.) route of injection, SJL and NZW mice (s and z alleles, respectively) had shorter incubation periods than C57BL mice (b allele) at several concentrations of two scrapie strains, ME7 and 139A. The three mouse strains have the same Sinc genotype, s7s7. Incubation period data among the three mouse strains after intraperitoneal (i.p.) injection revealed a different rank order of incubation periods from that seen after i.c. injection. End-point titers in the three mouse strains were similar after i.c. injection, but both scrapie strains yielded very low titers in NZW mice after i.p. injection. There were marked differences between 139A and ME7 incubation periods after both i.c. and i.p. injections in the three mouse genotypes, providing an additional parameter that distinguishes these two scrapie strains.
Insights
Mouse H-2D locus influences scrapie incubation. SJL and NZW mice showed shorter incubation periods than C57BL mice after intracerebral injection, but a different order after intraperitoneal injection.
Area of Science:
- Neuroscience
- Immunology
- Genetics
Background:
- The mouse H-2D locus is known to influence the incubation period of scrapie, a prion disease.
- Understanding genetic influences on prion disease pathogenesis is crucial for developing therapeutic strategies.
Purpose of the Study:
- To investigate the influence of the mouse H-2D locus on scrapie incubation periods using different scrapie strains and routes of inoculation.
- To compare the incubation periods and end-point titers in different mouse strains with identical Sinc genotypes.
Main Methods:
- Intracerebral (i.c.) and intraperitoneal (i.p.) injections of two scrapie strains (ME7 and 139A) into SJL, NZW, and C57BL mice.
- Monitoring and recording of scrapie incubation periods.
- Quantification of end-point titers in mouse brains.
Main Results:
- After i.c. injection, SJL (s allele) and NZW (z allele) mice exhibited shorter incubation periods than C57BL (b allele) mice for both scrapie strains.
- A different rank order of incubation periods was observed after i.p. injection compared to i.c. injection.
- End-point titers were similar across strains after i.c. injection, but significantly lower in NZW mice after i.p. injection.
- Distinct incubation period differences between ME7 and 139A strains were noted for both inoculation routes and all mouse genotypes.
Conclusions:
- The mouse H-2D locus significantly impacts scrapie incubation periods, with the route of inoculation altering the observed genetic influence.
- Scrapie strain-specific differences in incubation periods provide a valuable parameter for distinguishing strains and understanding disease dynamics.