Search

Cell cultures represent versatile and useful experimental models of transmissible spongiform encephalopathies. These models include chronically prion infected cell lines, as well as cultures expressing variable amounts of wild-type, mutated or chimeric prion proteins. These cultures have been widely used to investigate the biology of both the normal and the pathological isoform of the prion protein. They have also contributed to the comprehension of the pathogenic processes occurring in transmissible spongiform encephalopathies and in the development of new therapeutic approaches of these diseases. To cite this article: S. Lehmann et al., C. R. Biologies, 325 (2002) 59–65.

A strategy based upon the introduction of an adenovirus-SV40 plasmid into multipotential cells was designed to immortalize clones displaying properties of lineage stem cells. The murine 1C11 cell line behaves as a neuroepithelial progenitor. Upon appropriate induction, almost 100% of 1C11 precursor cells develop neurite extensions and convert into either serotonergic or noradrenergic neurons. The two mutually exclusive neuronal programs are autoregulated by serotonergic or adrenergic receptors. PrPc is constitutively expressed by 1C11 cells. Antibody-mediated cross-linking of PrPc promotes the dephosphorylation of the tyrosine kinase Fyn associated to a Fyn kinase activation. The coupling of PrPc to Fyn is dependent on caveolin-1. It is restricted to the fully differentiated serotonergic or noradrenergic cells and occurs mainly at neurites. Thus, PrPc may represent a signal transduction protein which may fine-tune neuronal functions. Since the 1C11 stem cell supports prion replication, it may provide a tool to investigate whether PrPSc accumulation interferes with PrPc signalling activity.

Cell cultures represent versatile and useful experimental models of transmissible spongiform encephalopathies. These models include chronically prion infected cell lines, as well as cultures expressing variable amounts of wild-type, mutated or chimeric prion proteins. These cultures have been widely used to investigate the biology of both the normal and the pathological isoform of the prion protein. They have also contributed to the comprehension of the pathogenic processes occurring in transmissible spongiform encephalopathies and in the development of new therapeutic approaches of these diseases.