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Normal neurogenesis and scrapie pathogenesis in neural grafts lacking the prion protein homologue Doppel
Author(s) -
Behrens Axel,
Brandner Sebastian,
Genoud Nicolas,
Aguzzi Adriano
Publication year - 2001
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.1093/embo-reports/kve088
Subject(s) - scrapie , spongiosis , biology , neurogenesis , gliosis , embryonic stem cell , microbiology and biotechnology , virology , neural stem cell , phenotype , prion protein , gene , genetics , pathology , immunology , stem cell , neuroscience , disease , medicine
The agent that causes prion diseases is thought to be identical to PrP Sc , a conformer of the normal prion protein PrP C . Recently a novel protein, termed Doppel (Dpl), was identified that shares significant biochemical and structural homology with PrP C . 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 PrP C ‐deficient Prnp 0/0 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 PrP Sc accumulation, were observed. Therefore, Dpl is unlikely to exert a cell‐autonomous function during neural differentiation and, in contrast to its homologue PrP C , is dispensable for prion disease progression and for generation of PrP Sc .