A novel erythroid-specific marker of transmissible spongiform encephalopathies.
Transmissible spongiform encephalopathies (TSE) are a group of invariably fatal neurodegenerative diseases and include scrapie in sheep, bovine spongiform encephalopathy (BSE) in cattle, chronic wasting disease in deer and elk, and Kuru disease, Creutzfeldt-Jakob disease (CJD) and variant CJD in humans. The pathological effects of disease occur predominantly in the CNS (central nervous system), where common hallmarks include vacuolation, gliosis, accumulation of a protease-resistant, abnormally folded isoform of the prion protein (PrPSc) and neuronal cell death. Lack of understanding of the molecular mechanisms underlying disease pathogenesis, particularly in non-CNS tissues, means that there are currently no effective strategies for early diagnosis or therapeutic intervention of TSEs. Here we report the first identification of a molecular marker that is easily detectable in readily accessible tissues. We demonstrate that a dramatic decrease in expression of a transcript specific to erythroid lineage cells is a common feature of TSEs. Our findings indicate a previously unrecognized role for involvement of the erythroid lineage in the etiology of TSE pathogenesis and should provide a new focus for research into diagnostic and therapeutic strategies.
Miele
G
G
Division of Gene Expression and Development, Roslin Institute, Roslin, Midlothian, Scotland, UK.
Manson
J
J
Clinton
M
M
D028341:Activins; D000818:Animals; D015415:Biomarkers; D002460:Cell Line; D006801:Humans; D007265:Inhibins / Q000235:genetics; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D017096:Prion Diseases / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D011328:Prions / Q000235:genetics / Q000378:metabolism
D015415:Biomarkers; D011328:Prions; D028341:Activins; D007265:Inhibins