NR ANUY
AU Miele,G.; Alejo Blanco,A.R.; Baybutt,H.N.; Horvat,S.; Manson,J.; Clinton,M.
TI Embryonic activation and developmental expression of the murine prion protein gene
QU Gene Expression 2003; 11(1): 1-12
PT journal article
AB While it is well established that cellular prion protein (PrPc) expression is required for the development of transmissible spongiform encephalopathies (TSEs), the physiological function of PrPc has yet to be determined. A number of studies have examined PrP expression in different tissues and in the later stages of embryonic development. However, the relative levels of expression of PrP RNA and protein in tissues outside the central nervous system (CNS) is not well documented and the exact point of transcriptional activation of PrP during embryogenesis is unknown. We have studied PrP mRNA expression in murine embryos and both mRNA and protein expression in a variety of adult tissues. PrP RNA was detected at different levels in all tissues tested while PrPc protein was detectable in all adult tissues tested with the exception of kidney and liver. RNA and protein levels were also assessed at four points during postnatal brain development and levels of both were seen to increase with development. We also established that, during embryogenesis, induction of PrP RNA expression occurs between E8.5 and E9, during the period of transition from anaerobic to aerobic metabolism. Preliminary experiments investigating the effects of superoxide radicals on PrP expression in cultured neuroblastoma and astrocyte cells support the suggestion that PrPc forms part of a cellular antioxidant defense mechanism.
MH Aging/genetics/metabolism; Animals; Animals, Newborn; Antioxidants/metabolism; Brain/embryology/growth & development/metabolism; Cell Differentiation/drug effects/genetics; Cells, Cultured; Embryo/embryology/*metabolism; Energy Metabolism/genetics; Fetus; Gene Expression Regulation, Developmental/drug effects/*genetics; Mice; Mice, Inbred C57BL; Mice, Knockout; Oxidative Stress/drug effects/genetics; PrPc Proteins/drug effects/genetics/*metabolism; Prion Diseases/*genetics; RNA, Messenger/drug effects/metabolism; Superoxides/pharmacology; Support, Non-U.S. Gov't; Trans-Activation (Genetics)/drug effects/*genetics; Viscera/embryology/*metabolism
AD Department of Gene Expression & Development Roslin Institute, Roslin, Midlothian, Scotland, EH2S 9PS, UK
SP englisch
PO USA