PMC:3091645 / 1675-4616 JSONTXT

{"project":"2_test","denotations":[{"id":"20649983-17585315-10169575","span":{"begin":140,"end":141},"obj":"17585315"},{"id":"20649983-19399233-10169576","span":{"begin":142,"end":143},"obj":"19399233"},{"id":"20649983-6801762-10169577","span":{"begin":354,"end":355},"obj":"6801762"},{"id":"20649983-1346470-10169578","span":{"begin":497,"end":498},"obj":"1346470"},{"id":"20649983-18391177-10169579","span":{"begin":805,"end":806},"obj":"18391177"},{"id":"20649983-19767651-10169580","span":{"begin":807,"end":808},"obj":"19767651"},{"id":"20649983-1353438-10169581","span":{"begin":910,"end":911},"obj":"1353438"},{"id":"20649983-12691521-10169581","span":{"begin":910,"end":911},"obj":"12691521"},{"id":"20649983-17292334-10169581","span":{"begin":910,"end":911},"obj":"17292334"},{"id":"20649983-1373228-10169582","span":{"begin":939,"end":941},"obj":"1373228"},{"id":"20649983-7999308-10169583","span":{"begin":942,"end":944},"obj":"7999308"},{"id":"20649983-17195841-10169584","span":{"begin":955,"end":957},"obj":"17195841"},{"id":"20649983-18951376-10169585","span":{"begin":969,"end":971},"obj":"18951376"},{"id":"20649983-11823413-10169586","span":{"begin":1206,"end":1208},"obj":"11823413"},{"id":"20649983-18632556-10169587","span":{"begin":1209,"end":1211},"obj":"18632556"},{"id":"20649983-9568713-10169588","span":{"begin":1334,"end":1336},"obj":"9568713"},{"id":"20649983-15452225-10169589","span":{"begin":1710,"end":1712},"obj":"15452225"},{"id":"20649983-15992767-10169589","span":{"begin":1710,"end":1712},"obj":"15992767"},{"id":"20649983-16700923-10169589","span":{"begin":1710,"end":1712},"obj":"16700923"},{"id":"20649983-17437544-10169589","span":{"begin":1710,"end":1712},"obj":"17437544"},{"id":"20649983-18315872-10169589","span":{"begin":1710,"end":1712},"obj":"18315872"},{"id":"20649983-18082765-10169589","span":{"begin":1710,"end":1712},"obj":"18082765"},{"id":"20649983-19057641-10169589","span":{"begin":1710,"end":1712},"obj":"19057641"},{"id":"20649983-19308092-10169589","span":{"begin":1710,"end":1712},"obj":"19308092"},{"id":"20649983-17612632-10169590","span":{"begin":2079,"end":2081},"obj":"17612632"},{"id":"20649983-15672681-10169590","span":{"begin":2079,"end":2081},"obj":"15672681"},{"id":"20649983-10880376-10169590","span":{"begin":2079,"end":2081},"obj":"10880376"},{"id":"20649983-18537284-10169591","span":{"begin":2346,"end":2348},"obj":"18537284"},{"id":"20649983-18580573-10169592","span":{"begin":2379,"end":2381},"obj":"18580573"},{"id":"20649983-18580573-10169593","span":{"begin":2714,"end":2716},"obj":"18580573"}],"text":"Background\nThe pivotal role that the prion protein (PrP) plays in transmissible spongiform encephalopathies (TSE) is now well established [[1,2] for recent reviews]. The conversion of this host-encoded protein to an abnormal, partially proteinase K resistant, isoform is a hallmark of most TSEs and PrP is the only known constituent of mammalian prions [3]. The Prnp gene that encodes for PrP, is expressed in a broad range of vertebrate tissues but most abundantly in the central nervous system [4].\nAlthough PrP is evolutionary conserved, suggesting that it has an important role, its physiological function remains unclear even though its implication in neuroprotection, response to oxidative stress, cell proliferation and differentiation, synaptic function and signal transduction has been proposed [5,6]. Its temporal regulation led also to suspect an implication of this protein in early embryogenesis [7-9] but Prnp-knockout mice [10,11], cattle [12] and goat [13] were obtained with no drastic developmental phenotype and only subtle alterations of their circadian rhythm, hippocampal function and of their behavior. A similar observation was made when this gene was invalidated in adult neurons [14,15]. To explain these data, it was hypothesized that another host-encoded protein is able to compensate for the lack of PrP [16]. However, this protein has not yet been identified.\nTranscriptomic analysis has emerged as a powerful tool to decipher cellular pathways that are modified following a gene expression alteration as it does not pre-require the need of restricting hypothesis. Such approaches have been conducted to analyze the mechanisms underlying prion replication and neurotoxicity [see [17-24] for recent examples]. The obtained results appeared however inconsistent and closely related to the cell type and/or strain and animal model used, leading to difficulties in identifying the metabolic pathways involved.\nFewer studies have used a similar approach to try to understand the biological function of the PrP protein in immortalized non-neuronal cells [25-27]. The obtained results appear again to correlate with the cell line used as experimental model and no shared pathway has emerged from the comparison of these different experiments. In parallel, proteomic studies have been conducted either using two cell lines [28] or transgenic knockout mice [29]. While different sets of proteins were found to be affected by the PrP expression level in cells according to their origin, no significant difference was detected in the brain proteome of the analyzed 129/Sv-C57/Bl6 transgenic mice, bearing in mind that variations occurring for low abundant proteins might not have been detected [29].\nIn the present study, we report the comparisons of the whole brain transcriptomes of PrP knockout or wild type mice, both on an FVB/N genetic background, and of that of mice invalidated for the Prnp locus in adult neurons."}