Profiling Trait Anxiety Transcriptome Analysis Reveals Cathepsin B (Ctsb) as a Novel Candidate Gene for Emotionality in Mice 英文参考文献.docVIP

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Profiling Trait Anxiety Transcriptome Analysis Reveals Cathepsin B (Ctsb) as a Novel Candidate Gene for Emotionality in Mice 英文参考文献.doc

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Profiling Trait Anxiety Transcriptome Analysis Reveals Cathepsin B (Ctsb) as a Novel Candidate Gene for Emotionality in Mice 英文参考文献

ProfilingTraitAnxiety:TranscriptomeAnalysisReveals CathepsinB(Ctsb)asaNovelCandidateGenefor EmotionalityinMice LudwigCzibere1*,LauraA.Baur1¤a,AnkeWittmann1,KatjaGemmeke1,AndreaSteiner1,PeterWeber1, BennoPu¨tz1,NafeesAhmad1,2,MirjamBunck1,CorneliaGraf1,2,ReginaWidner1,ClaudiaKu¨hne1, MarkusPanhuysen3,BorisHambsch1,GabrieleRieder4¤b,ThomasReinheckel5,ChristophPeters5, FlorianHolsboer1,RainerLandgraf1,JanM.Deussing1,2 1Max Planck Institute of Psychiatry, Munich, Germany, 2Helmholtz Zentrum Mu¨nchen, Institute of Developmental Genetics, Neuherberg, Germany, 3Affectis Pharmaceuticals, Martinsried, Germany, 4Max von Pettenkofer Institute, Ludwig Maximilians University, Munich, Germany, 5Institute of Molecular Medicine and Cell Research,FacultyofBiology,AlbertLudwigsUniversity,Freiburg,Germany Abstract Behavioral endophenotypes are determined by a multitude of counteracting but precisely balanced molecular and physiological mechanisms. In this study, we aim to identify potential novel molecular targets that contribute to the multigenictrait‘‘anxiety’’.Weusedmicroarraystoinvestigatethegeneexpressionprofilesofdifferentbrainregionswithin thelimbicsystemofmicewhichwereselectivelybredforeitherhigh(HAB)orlow(LAB)anxiety-relatedbehavior,andalso showsigns ofcomorbid depression-like behavior. We identifiedandconfirmed sex-independentdifferences inthebasal expression of 13 candidate genes, using tissue from the entire brain, including coronin 7 (Coro7), cathepsin B (Ctsb), muscleblind-like 1 (Mbnl1), metallothionein 1 (Mt1), solute carrier family 25 member 17 (Slc25a17), tribbles homolog 2 (Trib2), zinc finger protein 672 (Zfp672), syntaxin 3 (Stx3), ATP-binding cassette, sub-family A member 2 (Abca2), ectonucleotide pyrophosphatase/phosphodiesterase 5 (Enpp5), high mobility group nucleosomal binding domain 3 (Hmgn3) and pyruvate dehydrogenase beta (Pdhb). Additionally, we confirmed brain region-specific differences in the expressionofsynaptotagmin4(Syt4). Ouridentificationofabou