Prion protein (PrP) gene-knockout cell lines: insight into functions of the PrP

Abstract

Elucidation of prion protein (PrP) functions is crucial to fully understand prion diseases. A major approach to studying PrP functions is the use of PrP gene-knockout (Prnp−/−) mice. So far, six types of Prnp−/− mice have been generated, demonstrating the promiscuous functions of PrP. Recently, other PrP family members, such as Doppel and Shadoo, have been found. However, information obtained from comparative studies of structural and functional analyses of these PrP family proteins do not fully reveal PrP functions. Recently, varieties of Prnp−/− cell lines established from Prnp−/− mice have contributed to the analysis of PrP functions. In this mini-review, we focus on Prnp−/− cell lines and summarize currently available Prnp−/− cell lines and their characterizations. In addition, we introduce the recent advances in the methodology of cell line generation with knockout or knockdown of the PrP gene. We also discuss how these cell lines have provided valuable insights into PrP functions and show future perspectives.

Low Stress Ion Conductance Microscopy of Sub-Cellular Stiffness

“…We estimate that for HN cells the cortex is 10.9 ± 0.5 μm at 213 ± 44 Pa plus 0.30 ± 0.05 μm slack at 3.7 ± 0.5 Pa. For HpL cells the cortex is 8.1 ± 0.4 μm at 320 ± 37 Pa plus 0.40 ± 0.03 μm slack at 7.9 ± 1.1 Pa. The different characteristics of slack in HpL cells may be related to absence of PrP or to ectopic expression of Dpl, 18 and hence to ataxia in HpL mice. 18 …”

“…The different characteristics of slack in HpL cells may be related to absence of PrP or to ectopic expression of Dpl, 18 and hence to ataxia in HpL mice. 18 …”

Prion protein PrP nucleic acid binding and mobilization implicates retroelements as the replicative component of transmissible spongiform encephalopathy

“…PrP has been ascribed multiple functions, ranging from synaptic plasticity to cell-surface signaling, cell-cell communication, and RNA metabolism (reviewed in references [21,22]). However, laboratory-raised Prnp-mutant mice display only subtle deficits, often irreproducible, in part because in four of six lines the knockout led to pathogenic upregulation of the adjacent Doppel (Prnd) gene, explaining many discrepancies (reviewed in reference [23]). Indeed, there has been little consensus about the physiological role of PrP, and its primary function has remained elusive.…”

In utero transmission and tissue distribution of chronic wasting disease-associated prions in free-ranging Rocky Mountain elk

“…Many interesting and confounding aspects of TSEs have been revealed, such as the fact that the causative agent is a prion (Prusiner, 1982), a misfolded, protease-resistant form (PrP res ) of a protein with nearly universal expression in the animal kingdom (PrP C ), and whose function is still elusive and controversial, despite the enormous body of research undertaken to reveal it (Aguzzi et al, 2008;Sakudo & Onodera, 2014).…”