Early Embryonic Gene Expression Profiling of Zebrafish Prion Protein (Prp2) Morphants 英文参考文献.docVIP

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Early Embryonic Gene Expression Profiling of Zebrafish Prion Protein (Prp2) Morphants 英文参考文献.doc

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Early Embryonic Gene Expression Profiling of Zebrafish Prion Protein (Prp2) Morphants 英文参考文献

EarlyEmbryonicGeneExpressionProfilingofZebrafish PrionProtein(Prp2)Morphants RasoulNourizadeh-Lillabadi,JacobSeil?Torgersen¤,OlavVestrheim,MelanieKo¨nig,PeterAlestro¨m, MohasinaSyed* DepartmentofBasicSciencesandAquaticMedicine,NorwegianSchoolofVeterinaryScience,Oslo,Norway Abstract Background: The Prion protein (PRNP/Prp) plays a crucial role in transmissible spongiform encephalopathies (TSEs) like Creutzfeldt-Jakob disease (CJD), scrapie and mad cow disease. Notwithstanding the importance in human and animal disease,fundamentalaspectsofPRNP/Prpfunctionandtransmissionremainsunaccountedfor. Methodology/Principal Findings: The zebrafish (Danio rerio) genome contains three Prp encoding genesassigned prp1, prp2andprp3.Currently,thesecondparalogueisbelievedtobethemostsimilartothemammalianPRNPgeneinstructure and function. Functional studies of the PRNP gene ortholog was addressed by prp2 morpholino (MO) knockdown experiments.InvestigationofPrp2depletedembryosrevealedhighmortalityandapoptosisat24hourspostfertilization (hpf)aswellasimpairedbrainandneuronaldevelopment.Inordertoelucidatetheunderlyingmechanisms,agenome- widetranscriptomeanalysiswascarriedoutinviable24hpfmorphants.Theresultingchangesingeneexpressionprofiles revealed 249 differently expressed genes linked to biological processes like cell death, neurogenesis and embryonic development. Conclusions/Significance:ThecurrentstudycontributestotheunderstandingofbasicPrpfunctionsanddemonstratesthat the zebrafish is an excellent model to address the role of Prp in vertebrates. The gene knockdown of prp2 indicates an essential biological function for the zebrafish ortholog with a morphant phenotype that suggests a neurodegenerative actionandgeneexpression effectswhichareapoptosisrelatedandeffectsgenenetworks controllingneurogenesisand embryodevelopment. Citation:Nourizadeh-LillabadiR,Seil?TorgersenJ,VestrheimO,Ko¨nigM,Alestro¨mP,etal.(2010)EarlyEmbryonicGeneExpressionProfilingofZebrafishPrion Protein(Prp2)Morphant