The results of our novel approach, based on monitoring prion protein expression in animals from the same transgenic mouse line, suggest that the risk of transmission of atypical scrapie is intrinsically lower than that of classical scrapie or BSE, especially in relation to the expression level of the prion protein.
Although they were not observed in non-transgenic animals fig. 5J, K), the structures stained were overlapping but different in each mouse line, suggesting that the intronic promoter is likely to contain some brain-specific regulatory elements that are insufficient to confer full specificity.
Although the mechanisms by which tau might influence Aβ deposition require further investigation, our data demonstrating increased Aβ concentrations in a tauopathy mouse line suggest that the presence of pathological tau can increase Aβ.
For example, we observed that several transgenic immunodeficient mice (including IFN-γ−/− or IL-4−/− mice) had slightly elevated serum levels for other cytokines than those that were genetically ablated in the respective mouse line, suggesting an altered baseline inflammatory responsiveness in these transgenic breeding colonies [ 27].
Of note, in the latter study, there was still a substantial decrease in the number of apoptotic (TUNEL positive) cardiomyocytes in FADD dominant-negative mouse line, suggesting that forms of cell death other than apoptosis were contributing to the infarct size.
This set of results, from different mouse lines, suggests that it is not the fibrillar Aβ peptide sequestred in the plaque that is responsible for the cognitive deficit, but rather some other diffusible Aβ species [ 329], or, as suggested more recently, intracellular Aβ peptide.
Based on the phenotypic characteristics of the mouse line we suggest that ARTE10 is a mouse model well suited for studying amyloid-lowering therapies and presumably also for validation of new target candidates.
This variation is greater than between different wild-type mouse lines and suggests that overexpression of PrP causes disturbance to maintenance of isotope ratios at an individual level.
The presence of Ser487 and Ser543 phosphorylation on menin purified from a mouse β cell line suggest that these modifications are likely to be important in menin function in the neuroendocrine lineages.
However, BSE-L isolates unexpectedly showed transmission of a disease with some phenotypic features that resembled those of the BSE-C agent when inoculated in either transgenic mice expressing ovine PrP (28 ) or inbred wild-type mouse lines (25 ), suggesting that atypical bovine strains can modify their properties, at least after species barrier passages, converging with those of BSE-C.
