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

Mario Nuvolone, Mario Hermann, Silvia Sorce, Giancarlo Russo, Cinzia Tiberi, Petra Schwarz, Eric Minikel, Despina Sanoudou, Pawel Pelczar, Adriano Aguzzi

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    31 Citations (Scopus)


    Although its involvement in prion replication and neurotoxicity during transmissible spongiform encephalopathies is undisputed, the physiological role of the cellular prion protein (PrPC) remains enigmatic. A plethora of functions have been ascribed to PrPC 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 TAL EN-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 PrnpZH3/ZH3 mice failed to identify phenotypes previously described in non-co-isogenic Prnp-/- mice. However, aged PrnpZH3/ZH3 mice developed a chronic demyelinating peripheral neuropathy, confirming the crucial involvement of PrPC in peripheral myelin maintenance. This new line represents a rigorous genetic resource for studying the role of PrPC in physiology and disease.

    Original languageEnglish
    Pages (from-to)313-327
    Number of pages15
    JournalJournal of Experimental Medicine
    Issue number3
    Publication statusPublished - 1 Jan 2016


    ASJC Scopus subject areas

    • Immunology and Allergy
    • Immunology

    Cite this

    Nuvolone, M., Hermann, M., Sorce, S., Russo, G., Tiberi, C., Schwarz, P., Minikel, E., Sanoudou, D., Pelczar, P., & Aguzzi, A. (2016). Strictly co-isogenic C57BL/6J-Prnp-/- mice: A rigorous resource for prion science. Journal of Experimental Medicine, 213(3), 313-327.