NR ABEJ
AU Behrens,A.; Brandner,S.; Genoud,N.; Aguzzi,A.
TI Normal neurogenesis and scrapie pathogenesis in neural grafts lacking the prion protein homologue Doppel
QU EMBO Reports 2001 Apr; 2(4): 347-52
IA http://www.pubmedcentral.gov/articlerender.fcgi?tool=pubmed&pubmedid=11306558
PT journal article
AB The agent that causes prion diseases is thought to be identical to PrPsc, a conformer of the normal prion protein PrPc. Recently a novel protein, termed Doppel (Dpl), was identified that shares significant biochemical and structural homology with PrPc. To investigate the function of Dpl in neurogenesis and in prion pathology, we generated embryonic stem (ES) cells harbouring a homozygous disruption of the Prnd gene that encodes Dpl. After in vitro differentiation and grafting into adult brains of PrPc-deficient Prnp0/0 mice, Dpl-deficient ES cell-derived grafts contained all neural lineages analyzed, including neurons and astrocytes. When Prnd-deficient neural tissue was inoculated with scrapie prions, typical features of prion pathology including spongiosis, gliosis and PrPsc accumulation, were observed. Therefore, Dpl is unlikely to exert a cell-autonomous function during neural differentiation and, in contrast to its homologue PrPc, is dispensable for prion disease progression and for generation of PrPsc.
MH Animals; Brain/metabolism/pathology; Cell Differentiation; Embryo/cytology; Female; Genotype; Homozygote; Male; Mice; Mice, Inbred C57BL; Models, Genetic; Mutation; Neurons/metabolism/*physiology; Prions/*genetics/metabolism; Research Support, Non-U.S. Gov't; Scrapie/*genetics/*metabolism/pathology; Stem Cells/metabolism; Tissue Transplantation
AD Institute of Neuropathology, UniversitätsSpital Zürich, Schmelzbergstrasse 12, CH-8091 Zürich, Switzerland.
SP englisch
PO England