Spontaneous Generation of Prions and Transmissible PrP Amyloid in a Humanised Transgenic Mouse Model of A117V GSS
June 16, 2020 | Biology
Reading time: 1 minute
Freshly curated from PLOS Biology, Lab.Equipment brings you this article for your everyday Biology news fix.
by Emmanuel A. Asante, Jacqueline M. Linehan, Andrew Tomlinson, Tatiana Jakubcova, Shyma Hamdan, Andrew Grimshaw, Michelle Smidak, Asif Jeelani, Akin Nihat, Simon Mead, Sebastian Brandner, Jonathan D. F. Wadsworth, John Collinge
Inherited prion diseases are caused by autosomal dominant coding mutations in the human prion protein (PrP) gene (PRNP) and account for about 15% of human prion disease cases worldwide. The proposed mechanism is that the mutation predisposes to conformational change in the expressed protein, leading to the generation of disease-related multichain PrP assemblies that propagate by seeded protein misfolding. Despite considerable experimental support for this hypothesis, to-date spontaneous formation of disease-relevant, transmissible PrP assemblies in transgenic models expressing only mutant human PrP has not been demonstrated. Here, we report findings from transgenic mice that express human PrP 117V on a mouse PrP null background (117VV Tg30 mice), which model the PRNP A117V mutation causing inherited prion disease (IPD) including Gerstmann-Sträussler-Scheinker (GSS) disease phenotypes in humans. By studying brain samples from uninoculated groups of mice, we discovered that some mice (≥475 days old) spontaneously generated abnormal PrP assemblies, which after inoculation into further groups of 117VV Tg30 mice, produced a molecular and neuropathological phenotype congruent with that seen after transmission of brain isolates from IPD A117V patients to the same mice. To the best of our knowledge, the 117VV Tg30 mouse line is the first transgenic model expressing only mutant human PrP to show spontaneous generation of transmissible PrP assemblies that directly mirror those generated in an inherited prion disease in humans... Read more of this in the PLOS Biology Blog.
If you're in the Bio industry and are in need of quality Bio lab equipment for your basic and advanced applications, then you are in the right place. Lab.Equipment showcases a large variety of equipment for Biology labs. Shop our highly-recommended Biology products such as:
Get a hold of multiuse products for your specific application by shopping our inventory of products designed and built by major brands like:
You can also count on Lab.Equipment for a selection of premium equipment best-fit for applications including cannabis, veterinary, environmental, and more. Amplify your efficiency by shopping precise and accurate laboratory equipment here.