Engineered mouse strains develop rare prion diseases without the need for an infectious agent.

Susan Lindquist of the Whitehead Institute for Biomedical Research in Cambridge, Massachusetts, and her colleagues have created mouse models for two fatal human diseases caused by prions — misfolded proteins that spur other proteins to misfold. Creutzfeldt–Jakob disease and fatal familial insomnia affect different parts of the brain and arise from different mutations in the same gene. Rather than inserting mutated genes into the mouse genome — a tactic that ineffectively mimics the disease — the researchers mutated the prion gene in place.

Single amino-acid changes in the mouse prion protein caused the brain degeneration that is characteristic of each disease, and both models produce prions that can infect other mice.

Proc. Natl Acad. Sci. USA http://doi.org/njv (2013)