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

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

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
Volume213
Issue number3
DOIs
Publication statusPublished - 2016
Externally publishedYes

Fingerprint

Prions
129 Strain Mouse
Phenotype
Prion Diseases
Inbreeding
Peripheral Nervous System Diseases
Embryonic Stem Cells
Myelin Sheath
Oocytes
Alleles
Maintenance

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

Nuvolone, M., Hermann, M., Sorce, S., Russo, G., Tiberi, C., Schwarz, 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. https://doi.org/10.1084/jem.20151610

Strictly co-isogenic C57BL/6J-Prnp-/- mice : A rigorous resource for prion science. / Nuvolone, Mario; Hermann, Mario; Sorce, Silvia; Russo, Giancarlo; Tiberi, Cinzia; Schwarz, Petra; Minikel, Eric; Sanoudou, Despina; Pelczar, Pawel; Aguzzi, Adriano.

In: Journal of Experimental Medicine, Vol. 213, No. 3, 2016, p. 313-327.

Research output: Contribution to journalArticle

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, vol. 213, no. 3, pp. 313-327. https://doi.org/10.1084/jem.20151610
Nuvolone, Mario ; Hermann, Mario ; Sorce, Silvia ; Russo, Giancarlo ; Tiberi, Cinzia ; Schwarz, Petra ; Minikel, Eric ; Sanoudou, Despina ; Pelczar, Pawel ; Aguzzi, Adriano. / Strictly co-isogenic C57BL/6J-Prnp-/- mice : A rigorous resource for prion science. In: Journal of Experimental Medicine. 2016 ; Vol. 213, No. 3. pp. 313-327.
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