Quantitative gene expression profiling of mouse brain regions reveals differential transcripts conserved in human and affected in disease models
Identifieur interne : 000862 ( Hal/Curation ); précédent : 000861; suivant : 000863Quantitative gene expression profiling of mouse brain regions reveals differential transcripts conserved in human and affected in disease models
Auteurs : Camille Brochier [France]Source :
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Abstract
In order to get a better understanding of brain complexity at a molecular level, we explored the mouse brain transcriptome using the Serial Analysis of Gene Expression method. SAGE libraries were generated from 11 mouse brain territories, including six cortical regions, as well as the striatum, the nucleus accumbens, the thalamus, the substantia nigra, and the ventral tegmental area. The entire project delivered 1.2 million SAGE tags, allowing the detection of rare mRNAs. Comparison of all transcriptomes revealed 308 transcripts differentially expressed, a number of which have no documented function. We further analyzed the expression profiles by real-time RT-PCR or in situ hybridization (ISH). Since the brain is a heterogeneous organ, it was important to determine the cell types that are expressing the novel markers. A combination of in situ hybridization with immunohistochemistry showed the expression of 3 midbrain-enriched mRNAs in dopaminergic neurons. We tested whether mouse markers could be expressed in homologous regions in the human brain. There was a good overall conservation of expression patterns in both species. To evaluate the possibility that genes predominantly expressed in a given brain structure may indeed be relevant to its function, we studied pathophysiological conditions that target specific neuronal populations. Using quantitative RT-PCR, we so far measured the abundance of striatum- or cortex-enriched transcripts in the mouse R6/2 genetic model of Huntington's disease. Likewise, we showed the regulation of transcripts enriched in the striatum or substantia nigra in pharmacological rodent models of Parkinson's disease, in which the nigro-striatal dopaminergic pathway is disrupted.
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Likewise, we showed the regulation of transcripts enriched in the striatum or substantia nigra in pharmacological rodent models of Parkinson's disease, in which the nigro-striatal dopaminergic pathway is disrupted.</div></front></TEI><hal api="V3"> <titleStmt> <title xml:lang="en">Quantitative gene expression profiling of mouse brain regions reveals differential transcripts conserved in human and affected in disease models</title> <title xml:lang="fr">Analyse des transcriptomes du cerveau de souris : mise en évidence de patrons régionaux d'expression conservés chez l'homme et altérés dans des modèles de maladies neurodégénératives</title> <author role="aut"> <persName> <forename type="first">Camille</forename> <surname>Brochier</surname> </persName> <idno type="halauthorid">303369</idno> <affiliation ref="#struct-40438"></affiliation> </author> <editor role="depositor"> <persName> <forename>Celine</forename> <surname>Lentz</surname> </persName> <email type="md5">2ea2e4d9f9bc2759ef7181bf58a599b4</email> <email type="domain">cea.fr</email> </editor> </titleStmt> <editionStmt> <edition n="v1" type="current"> <date type="whenSubmitted">2009-02-13 13:03:07</date> <date type="whenModified">2016-01-21 15:20:31</date> <date type="whenReleased">2009-02-13 13:45:28</date> <date type="whenProduced">2007-09-21</date> <date type="whenEndEmbargoed">2009-02-13</date> <ref type="file" target="https://tel.archives-ouvertes.fr/tel-00361207/document"> <date notBefore="2009-02-13"></date> </ref> <ref type="file" n="1" target="https://tel.archives-ouvertes.fr/tel-00361207/file/These_Brochier_Camille_2007_CEA_iBiTecS.pdf.pdf"> <date notBefore="2009-02-13"></date> </ref> </edition> <respStmt> <resp>contributor</resp> <name key="121367"> <persName> <forename>Celine</forename> <surname>Lentz</surname> </persName> <email type="md5">2ea2e4d9f9bc2759ef7181bf58a599b4</email> <email type="domain">cea.fr</email> </name> </respStmt> </editionStmt> <publicationStmt> <distributor>CCSD</distributor> <idno type="halId">tel-00361207</idno> <idno type="halUri">https://tel.archives-ouvertes.fr/tel-00361207</idno> <idno type="halBibtex">brochier:tel-00361207</idno> <idno type="halRefHtml">Sciences du Vivant [q-bio]. Université Paris Sud - Paris XI, 2007. Français</idno> <idno type="halRef">Sciences du Vivant [q-bio]. Université Paris Sud - Paris XI, 2007. Français</idno> </publicationStmt> <seriesStmt> <idno type="stamp" n="CEA">CEA - Commissariat à l'énergie atomique</idno> <idno type="stamp" n="DSV" p="CEA">Direction des sciences du vivant</idno> </seriesStmt> <notesStmt></notesStmt> <sourceDesc> <biblStruct> <analytic> <title xml:lang="en">Quantitative gene expression profiling of mouse brain regions reveals differential transcripts conserved in human and affected in disease models</title> <title xml:lang="fr">Analyse des transcriptomes du cerveau de souris : mise en évidence de patrons régionaux d'expression conservés chez l'homme et altérés dans des modèles de maladies neurodégénératives</title> <author role="aut"> <persName> <forename type="first">Camille</forename> <surname>Brochier</surname> </persName> <idno type="halauthorid">303369</idno> <affiliation ref="#struct-40438"></affiliation> </author> </analytic> <monogr> <imprint> <date type="dateDefended">2007-09-21</date> </imprint> <authority type="institution">Université Paris Sud - Paris XI</authority> <authority type="supervisor">Jean-Marc Elalouf(jean-marc.elalouf@cea.fr)</authority> <authority type="jury">Monique Bolotin-Fukuhara Présidente</authority> <authority type="jury">Brigitte Kieffer Rapporteuse</authority> <authority type="jury">Gilbert Vassart Rapporteur</authority> <authority type="jury">Tania Vitalis Examinatrice</authority> <authority type="jury">Jean-Marc Elalouf Directeur de thèse</authority> </monogr> </biblStruct> </sourceDesc> <profileDesc> <langUsage> <language ident="fr">French</language> </langUsage> <textClass> <keywords scheme="author"> <term xml:lang="en">biological markers</term> <term xml:lang="en">capucin</term> <term xml:lang="en">neurodegenerative diseases</term> <term xml:lang="en">serial analysis of
gene expression</term> <term xml:lang="fr">marqueurs biologiques</term> <term xml:lang="fr">capucine</term> <term xml:lang="fr">maladies neurodégénératives</term> <term xml:lang="fr">analyse en série de l'expression des gènes</term> <term xml:lang="fr">Tmem90a</term> </keywords> <classCode scheme="halDomain" n="sdv">Life Sciences [q-bio]</classCode> <classCode scheme="halTypology" n="THESE">Theses</classCode> </textClass> <abstract xml:lang="en">In order to get a better understanding of brain complexity at a molecular level, we explored the mouse brain transcriptome using the Serial Analysis of Gene Expression method. SAGE libraries were generated from 11 mouse brain territories, including six cortical regions, as well as the striatum, the nucleus accumbens, the thalamus, the substantia nigra, and the ventral tegmental area. The entire project delivered 1.2 million SAGE tags, allowing the detection of rare mRNAs. Comparison of all transcriptomes revealed 308 transcripts differentially expressed, a number of which have no documented function. We further analyzed the expression profiles by real-time RT-PCR or in situ hybridization (ISH). Since the brain is a heterogeneous organ, it was important to determine the cell types that are expressing the novel markers. A combination of in situ hybridization with immunohistochemistry showed the expression of 3 midbrain-enriched mRNAs in dopaminergic neurons. We tested whether mouse markers could be expressed in homologous regions in the human brain. There was a good overall conservation of expression patterns in both species. To evaluate the possibility that genes predominantly expressed in a given brain structure may indeed be relevant to its function, we studied pathophysiological conditions that target specific neuronal populations. Using quantitative RT-PCR, we so far measured the abundance of striatum- or cortex-enriched transcripts in the mouse R6/2 genetic model of Huntington's disease. Likewise, we showed the regulation of transcripts enriched in the striatum or substantia nigra in pharmacological rodent models of Parkinson's disease, in which the nigro-striatal dopaminergic pathway is disrupted.</abstract> <abstract xml:lang="fr">L'analyse à grande échelle de l'expression des gènes dans le cerveau est une approche puissante et relativement nouvelle, susceptible d'identifier des gènes candidats pour l'analyse des fonctions cérébrales. Nous avons utilisé la méthode Serial Analysis of Gene Expression pour établir un profil d'expression quantitatif de 11 régions du cerveau de souris, dont plusieurs régions corticales, le noyau accumbens, le striatum, le thalamus, la substance noire et l'aire tegmentale ventrale. Plus d'un million d'étiquettes SAGE ont été générées, permettant la détection de transcrits peu abondants. La comparaison des banques SAGE a mis en évidence 308 gènes différentiellement exprimés dans le cerveau de souris, dont la majorité n'a pas de fonction connue. Ces données ont été validées par la RT-PCR quantitative ou l'hybridation in situ (HIS). Le cerveau étant un organe de composition hétérogène, nous avons utilisé une technique combinant l'HIS et l'immunohistochimie afin d'étudier la distribution cellulaire des ARNm de trois marqueurs mésencéphaliques. Nous avons également entrepris d'étendre à l'homme les analyses d'expression réalisées chez la souris. Nos données montrent que les patterns d'expression génique entre des régions comparables du cerveau humain et du cerveau murin sont généralement conservés. Par ailleurs, nous nous sommes interrogés sur la régulation des gènes différentiellement exprimés dans un contexte physiopathologique affectant des régions cérébrales spécifiques. Ainsi, nous avons montré la régulation de plusieurs marqueurs striataux, corticaux et mésencéphaliques dans des modèles murins des maladies de Huntington et Parkinson.</abstract> </profileDesc> </hal></record>Pour manipuler ce document sous Unix (Dilib)
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