Transgenic mouse brains for the evaluation and quality control of BSE tests

Abstract

Rapid BSE tests are widely used diagnostics in veterinary medicine and more than 11 million tests are applied worldwide. The evaluation of new rapid BSE tests and the quality assurance of approved BSE tests pose a challenge owing to the natural scarcity of BSE-infected bovine brainstems and regional variations in prion titer. Transgenic mice expressing bovine prion protein (Tg4092) offer an alternative approach to these problems. To determine whether BSE-infected Tg4092 mouse brains could serve as a general standard for rapid BSE tests, we inoculated Tg4092 mice intracerebrally with BSE prions, harvested brains at defined time points post-infection and analyzed cerebral hemispheres with several approved rapid BSE tests. The results show that de novo formation of the disease-causing prion protein isoform, PrP(Sc), can be monitored during the course of infection. We demonstrate that BSE-infected Tg4092 mouse brains provide a renewable and controllable source of reference samples and suggest that such samples can generally be used for the evaluation and quality control of rapid BSE tests.

Resistance of Bovine Spongiform Encephalopathy (BSE) Prions to Inactivation

“…A more suitable model for BSE prions may be BSE passaged in Tg(BoPrP) mice, which produce PrP Sc with the BoPrP sequence as well as with the same electrophoretic mobility and glycosylation pattern as cattle BSE prions [58]. Infected brains from this line were recently shown to be suitable for evaluation of BSE tests [59]. However, these bovine prions are in the milieu of mouse brain homogenate rather than cattle brain homogenate, and it remains to be determined whether this has an effect on the inactivation characteristics.…”

Non‐Adhesive Behavior of New Nanostructured PNIPAM Surfaces Towards Specific Neurodegenerative Proteins: Application to Storage and Titration of Tau Proteins

“…Their presence is difficult to monitor, specifically in different body fluids like blood and cerebrospinal fluid (CSF) 2, 3. Standard immunoenzymatic tests are not sensitive enough to give reliable identification in the ante mortem stage due to the extremely low concentrations of these proteins 4–7. Moreover, Perret‐Liaudet et al8 noticed a great loss of phosphorylated Tau protein (pTau181), Tau, and Aβ‐42 peptide on the inner walls of sampling tubes with time, leading to false titration values.…”

Conformation-Dependent High-Affinity Monoclonal Antibodies to Prion Proteins

“…More importantly, immunoassays of brainstems from cattle destined for the human food supply have helped reduce exposure of people to bovine prions (10). Compelling evidence has accumulated that vCJD results from the consumption of prion-infected bovine tissue (11–13), but fortunately, cases of vCJD are dwindling.…”