| First Author | Nuvolone M | Year | 2016 |
| Journal | J Exp Med | Volume | 213 |
| Issue | 3 | Pages | 313-27 |
| PubMed ID | 26926995 | Mgi Jnum | J:233015 |
| Mgi Id | MGI:5780613 | Doi | 10.1084/jem.20151610 |
| Citation | Nuvolone M, et al. (2016) Strictly co-isogenic C57BL/6J-Prnp-/- mice: A rigorous resource for prion science. J Exp Med 213(3):313-27 |
| abstractText | 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. |
