Strictly co-isogenic C57BL/6J-Prnp-/- mice: A rigorous resource for prion science


Nuvolone M, Hermann M, Sorce S, Russo G, Tiberi C, Schwarz P, Minikel E, Sanoudou D, Pelczar P, Aguzzi A. Strictly co-isogenic C57BL/6J-Prnp-/- mice: A rigorous resource for prion science. J Exp MedJ Exp MedJ Exp Med. 2016;213:313-27.


Although its involvement in prion replication and neurotoxicity during transmissible spongiform encephalopathies is undisputed, the physiological role of the cellular prion protein (PrP(C)) remains enigmatic. A plethora of functions have been ascribed to PrP(C) based on phenotypes of Prnp(-/-) mice. However, all currently available Prnp(-/-) lines were generated in embryonic stem cells from the 129 strain of the laboratory mouse and mostly crossed to non-129 strains. Therefore, Prnp-linked loci polymorphic between 129 and the backcrossing strain resulted in systematic genetic confounders and led to erroneous conclusions. We used TALEN-mediated genome editing in fertilized mouse oocytes to create the Zurich-3 (ZH3) Prnp-ablated allele on a pure C57BL/6J genetic background. Genomic, transcriptional, and phenotypic characterization of Prnp(ZH3/ZH3) mice failed to identify phenotypes previously described in non-co-isogenic Prnp(-/-) mice. However, aged Prnp(ZH3/ZH3) mice developed a chronic demyelinating peripheral neuropathy, confirming the crucial involvement of PrP(C) in peripheral myelin maintenance. This new line represents a rigorous genetic resource for studying the role of PrP(C) in physiology and disease.


Nuvolone, MarioHermann, MarioSorce, SilviaRusso, GiancarloTiberi, CinziaSchwarz, PetraMinikel, EricSanoudou, DespinaPelczar, PawelAguzzi, AdrianoengResearch Support, Non-U.S. Gov't2016/03/02 06:00J Exp Med. 2016 Mar 7;213(3):313-27. doi: 10.1084/jem.20151610. Epub 2016 Feb 29.