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

J Exp Med. 2016 Mar 7;213(3):313-27. doi: 10.1084/jem.20151610. Epub 2016 Feb 29.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Chromosomes, Mammalian
  • Endonucleases / metabolism
  • Female
  • Gene Deletion
  • Macrophages / metabolism
  • Male
  • Mice, Inbred C57BL
  • Molecular Sequence Data
  • Nerve Degeneration / pathology
  • Open Reading Frames / genetics
  • Phagocytosis
  • Phenotype
  • Polyradiculoneuropathy / pathology
  • Prions / metabolism*
  • RNA / metabolism
  • Sequence Analysis, RNA
  • Trans-Activators / genetics


  • Prions
  • Trans-Activators
  • RNA
  • Endonucleases