Abstract
The major determinant of prion disease incubation time in mice is thought to be the amino acid sequence of the prion protein. Two alleles of the mouse prion gene (Prnp) have been described, where Prnp a (Leu-108, Thr-189) and Prnp b (Phe-108, Val-189) are associated with short and long incubation times, to defined prion strains, respectively. As part of a survey of inbred mouse lines, the prion gene open reading frame was sequenced and revealed a new allele, Prnp c (Phe-108, Thr-189), in the strain MAI/Pas. To study the influence of Prnp c independently of the MAI/Pas genetic background, we generated a congenic line in which Prnp c was bred onto the C57BL/6JOlaHsd background. Following intracerebral inoculation with Chandler/RML scrapie prions, the congenic mice showed an increased mean incubation time relative to C57BL/6JOlaHsd, of over 100 days. However, no differences were observed in the intensity and pattern of PrP immunoreactivity deposition or spongiosis. We conclude that the new allele, Prnp c, modulates incubation time but not neuropathology and that the previous classification of mice into two distinct groups based on incubation time and Prnp genotype should now be revised.
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Acknowledgments
We are very grateful to Jean-Louis Guénet for the kind gift of MAI/Pas and PWK/Pas mice and to Bruce Cattanach for JU/FaCt mice. We also thank Catherine O’Malley, Paul Hudson, and Judy Beake for preparation of histological slides and Katie Fox for preparation of brain homogenates for Western blotting. In addition, we thank Dave Moore and team for animal care and Ray Young for preparation of figures. This work was supported by the Medical Research Council, UK.
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Lloyd, S.E., Thompson, S.R., Beck, J.A. et al. Identification and characterization of a novel mouse prion gene allele. Mamm Genome 15, 383–389 (2004). https://doi.org/10.1007/s00335-004-3041-5
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DOI: https://doi.org/10.1007/s00335-004-3041-5