Modeling the monosomy for the telomeric part of human chromosome 21 reveals haploinsufficient genes modulating the inflammatory and airway responses
Identifieur interne : 001321 ( Istex/Corpus ); précédent : 001320; suivant : 001322Modeling the monosomy for the telomeric part of human chromosome 21 reveals haploinsufficient genes modulating the inflammatory and airway responses
Auteurs : Vanessa Besson ; Vronique Brault ; Arnaud Duchon ; Dieudonn Togbe ; Jean-Charles Bizot ; Valrie F. J. Quesniaux ; Bernard Ryffel ; Yann HraultSource :
- Human Molecular Genetics [ 0964-6906 ] ; 2007-09-01.
Abstract
Monosomy 21 is a rare human disease due to gene dosage errors disturbing a variety of physiological and morphological systems including brain, skeletal, immune and respiratory functions. Most of the human condition corresponds to partial or mosaic monosomy suggesting that Monosomy 21 may be lethal. In order to search for dosage-sensitive genes involved in the human pathology, we generated by chromosomal engineering a monosomic mouse for the Prmt2Col6a1 interval corresponding to the most telomeric part of human chromosome 21. Haploinsufficiency of the 13 genes, located in the 0.5Mb genetic interval and conserved in man and mouse, caused apparently no morphological defect as observed in patients. However, monosomic mice displayed an enhanced inflammatory response after local intranasal lipopolysaccharide administration with enhanced recruitment of neutrophils and secretion of cytokines such as tumor necrosis factor- (TNF-), IL-1, IL-12p70 and IFN- in the lung as well increased TNF- production after systemic administration. Further analysis demonstrates that monosomic macrophages were involved and that a few genes, Prmt2, Pcnt2, Mcm3ap and Lss located in the region were candidate for the inflammatory response. Altogether, these results demonstrate the existence of dosage-sensitive genes in the Prmt2Col6a1 region that control the inflammation and the lung function. Furthermore, they point out that similar partial Monosomies 21 in human might have eluded the diagnosis due to the very specific defects observed in this murine model.
Url:
DOI: 10.1093/hmg/ddm152
Links to Exploration step
ISTEX:8F88D4D15114343F11E092A217F647CD4526280ALe document en format XML
<record><TEI wicri:istexFullTextTei="biblStruct"><teiHeader><fileDesc><titleStmt><title>Modeling the monosomy for the telomeric part of human chromosome 21 reveals haploinsufficient genes modulating the inflammatory and airway responses</title><author><name sortKey="Besson, Vanessa" sort="Besson, Vanessa" uniqKey="Besson V" first="Vanessa" last="Besson">Vanessa Besson</name><affiliation><mods:affiliation>Institut de Transgenose, Molecular Immunology and Embryology, UMR6218, CNRS, Universit Orlans, 3B rue de la Frollerie, Orlans, Cedex 2 45071, France and</mods:affiliation></affiliation></author><author><name sortKey="Brault, Vronique" sort="Brault, Vronique" uniqKey="Brault V" first="Vronique" last="Brault">Vronique Brault</name><affiliation><mods:affiliation>Institut de Transgenose, Molecular Immunology and Embryology, UMR6218, CNRS, Universit Orlans, 3B rue de la Frollerie, Orlans, Cedex 2 45071, France and</mods:affiliation></affiliation></author><author><name sortKey="Duchon, Arnaud" sort="Duchon, Arnaud" uniqKey="Duchon A" first="Arnaud" last="Duchon">Arnaud Duchon</name><affiliation><mods:affiliation>Institut de Transgenose, Molecular Immunology and Embryology, UMR6218, CNRS, Universit Orlans, 3B rue de la Frollerie, Orlans, Cedex 2 45071, France and</mods:affiliation></affiliation></author><author><name sortKey="Togbe, Dieudonn" sort="Togbe, Dieudonn" uniqKey="Togbe D" first="Dieudonn" last="Togbe">Dieudonn Togbe</name><affiliation><mods:affiliation>Institut de Transgenose, Molecular Immunology and Embryology, UMR6218, CNRS, Universit Orlans, 3B rue de la Frollerie, Orlans, Cedex 2 45071, France and</mods:affiliation></affiliation></author><author><name sortKey="Bizot, Jean Charles" sort="Bizot, Jean Charles" uniqKey="Bizot J" first="Jean-Charles" last="Bizot">Jean-Charles Bizot</name><affiliation><mods:affiliation>Key-Obs SA, 45150 Orlans, France</mods:affiliation></affiliation></author><author><name sortKey="Quesniaux, Valrie F J" sort="Quesniaux, Valrie F J" uniqKey="Quesniaux V" first="Valrie F. J." last="Quesniaux">Valrie F. J. Quesniaux</name><affiliation><mods:affiliation>Institut de Transgenose, Molecular Immunology and Embryology, UMR6218, CNRS, Universit Orlans, 3B rue de la Frollerie, Orlans, Cedex 2 45071, France and</mods:affiliation></affiliation></author><author><name sortKey="Ryffel, Bernard" sort="Ryffel, Bernard" uniqKey="Ryffel B" first="Bernard" last="Ryffel">Bernard Ryffel</name><affiliation><mods:affiliation>Institut de Transgenose, Molecular Immunology and Embryology, UMR6218, CNRS, Universit Orlans, 3B rue de la Frollerie, Orlans, Cedex 2 45071, France and</mods:affiliation></affiliation></author><author><name sortKey="Hrault, Yann" sort="Hrault, Yann" uniqKey="Hrault Y" first="Yann" last="Hrault">Yann Hrault</name><affiliation><mods:affiliation>Institut de Transgenose, Molecular Immunology and Embryology, UMR6218, CNRS, Universit Orlans, 3B rue de la Frollerie, Orlans, Cedex 2 45071, France and</mods:affiliation></affiliation><affiliation><mods:affiliation>E-mail: herault@cnrs-orleans.fr</mods:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">ISTEX</idno><idno type="RBID">ISTEX:8F88D4D15114343F11E092A217F647CD4526280A</idno><date when="2007" year="2007">2007</date><idno type="doi">10.1093/hmg/ddm152</idno><idno type="url">https://api.istex.fr/document/8F88D4D15114343F11E092A217F647CD4526280A/fulltext/pdf</idno><idno type="wicri:Area/Istex/Corpus">001321</idno></publicationStmt><sourceDesc><biblStruct><analytic><title level="a">Modeling the monosomy for the telomeric part of human chromosome 21 reveals haploinsufficient genes modulating the inflammatory and airway responses</title><author><name sortKey="Besson, Vanessa" sort="Besson, Vanessa" uniqKey="Besson V" first="Vanessa" last="Besson">Vanessa Besson</name><affiliation><mods:affiliation>Institut de Transgenose, Molecular Immunology and Embryology, UMR6218, CNRS, Universit Orlans, 3B rue de la Frollerie, Orlans, Cedex 2 45071, France and</mods:affiliation></affiliation></author><author><name sortKey="Brault, Vronique" sort="Brault, Vronique" uniqKey="Brault V" first="Vronique" last="Brault">Vronique Brault</name><affiliation><mods:affiliation>Institut de Transgenose, Molecular Immunology and Embryology, UMR6218, CNRS, Universit Orlans, 3B rue de la Frollerie, Orlans, Cedex 2 45071, France and</mods:affiliation></affiliation></author><author><name sortKey="Duchon, Arnaud" sort="Duchon, Arnaud" uniqKey="Duchon A" first="Arnaud" last="Duchon">Arnaud Duchon</name><affiliation><mods:affiliation>Institut de Transgenose, Molecular Immunology and Embryology, UMR6218, CNRS, Universit Orlans, 3B rue de la Frollerie, Orlans, Cedex 2 45071, France and</mods:affiliation></affiliation></author><author><name sortKey="Togbe, Dieudonn" sort="Togbe, Dieudonn" uniqKey="Togbe D" first="Dieudonn" last="Togbe">Dieudonn Togbe</name><affiliation><mods:affiliation>Institut de Transgenose, Molecular Immunology and Embryology, UMR6218, CNRS, Universit Orlans, 3B rue de la Frollerie, Orlans, Cedex 2 45071, France and</mods:affiliation></affiliation></author><author><name sortKey="Bizot, Jean Charles" sort="Bizot, Jean Charles" uniqKey="Bizot J" first="Jean-Charles" last="Bizot">Jean-Charles Bizot</name><affiliation><mods:affiliation>Key-Obs SA, 45150 Orlans, France</mods:affiliation></affiliation></author><author><name sortKey="Quesniaux, Valrie F J" sort="Quesniaux, Valrie F J" uniqKey="Quesniaux V" first="Valrie F. J." last="Quesniaux">Valrie F. J. Quesniaux</name><affiliation><mods:affiliation>Institut de Transgenose, Molecular Immunology and Embryology, UMR6218, CNRS, Universit Orlans, 3B rue de la Frollerie, Orlans, Cedex 2 45071, France and</mods:affiliation></affiliation></author><author><name sortKey="Ryffel, Bernard" sort="Ryffel, Bernard" uniqKey="Ryffel B" first="Bernard" last="Ryffel">Bernard Ryffel</name><affiliation><mods:affiliation>Institut de Transgenose, Molecular Immunology and Embryology, UMR6218, CNRS, Universit Orlans, 3B rue de la Frollerie, Orlans, Cedex 2 45071, France and</mods:affiliation></affiliation></author><author><name sortKey="Hrault, Yann" sort="Hrault, Yann" uniqKey="Hrault Y" first="Yann" last="Hrault">Yann Hrault</name><affiliation><mods:affiliation>Institut de Transgenose, Molecular Immunology and Embryology, UMR6218, CNRS, Universit Orlans, 3B rue de la Frollerie, Orlans, Cedex 2 45071, France and</mods:affiliation></affiliation><affiliation><mods:affiliation>E-mail: herault@cnrs-orleans.fr</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j">Human Molecular Genetics</title><idno type="ISSN">0964-6906</idno><idno type="eISSN">1460-2083</idno><imprint><publisher>Oxford University Press</publisher><date type="published" when="2007-09-01">2007-09-01</date><biblScope unit="volume">16</biblScope><biblScope unit="issue">17</biblScope><biblScope unit="page" from="2040">2040</biblScope><biblScope unit="page" to="2052">2052</biblScope></imprint><idno type="ISSN">0964-6906</idno></series><idno type="istex">8F88D4D15114343F11E092A217F647CD4526280A</idno><idno type="DOI">10.1093/hmg/ddm152</idno><idno type="ArticleID">ddm152</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0964-6906</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract">Monosomy 21 is a rare human disease due to gene dosage errors disturbing a variety of physiological and morphological systems including brain, skeletal, immune and respiratory functions. Most of the human condition corresponds to partial or mosaic monosomy suggesting that Monosomy 21 may be lethal. In order to search for dosage-sensitive genes involved in the human pathology, we generated by chromosomal engineering a monosomic mouse for the Prmt2Col6a1 interval corresponding to the most telomeric part of human chromosome 21. Haploinsufficiency of the 13 genes, located in the 0.5Mb genetic interval and conserved in man and mouse, caused apparently no morphological defect as observed in patients. However, monosomic mice displayed an enhanced inflammatory response after local intranasal lipopolysaccharide administration with enhanced recruitment of neutrophils and secretion of cytokines such as tumor necrosis factor- (TNF-), IL-1, IL-12p70 and IFN- in the lung as well increased TNF- production after systemic administration. Further analysis demonstrates that monosomic macrophages were involved and that a few genes, Prmt2, Pcnt2, Mcm3ap and Lss located in the region were candidate for the inflammatory response. Altogether, these results demonstrate the existence of dosage-sensitive genes in the Prmt2Col6a1 region that control the inflammation and the lung function. Furthermore, they point out that similar partial Monosomies 21 in human might have eluded the diagnosis due to the very specific defects observed in this murine model.</div></front></TEI><istex><corpusName>oup</corpusName><author><json:item><name>Vanessa Besson</name><affiliations><json:string>Institut de Transgenose, Molecular Immunology and Embryology, UMR6218, CNRS, Universit Orlans, 3B rue de la Frollerie, Orlans, Cedex 2 45071, France and</json:string></affiliations></json:item><json:item><name>Vronique Brault</name><affiliations><json:string>Institut de Transgenose, Molecular Immunology and Embryology, UMR6218, CNRS, Universit Orlans, 3B rue de la Frollerie, Orlans, Cedex 2 45071, France and</json:string></affiliations></json:item><json:item><name>Arnaud Duchon</name><affiliations><json:string>Institut de Transgenose, Molecular Immunology and Embryology, UMR6218, CNRS, Universit Orlans, 3B rue de la Frollerie, Orlans, Cedex 2 45071, France and</json:string></affiliations></json:item><json:item><name>Dieudonn Togbe</name><affiliations><json:string>Institut de Transgenose, Molecular Immunology and Embryology, UMR6218, CNRS, Universit Orlans, 3B rue de la Frollerie, Orlans, Cedex 2 45071, France and</json:string></affiliations></json:item><json:item><name>Jean-Charles Bizot</name><affiliations><json:string>Key-Obs SA, 45150 Orlans, France</json:string></affiliations></json:item><json:item><name>Valrie F.J. Quesniaux</name><affiliations><json:string>Institut de Transgenose, Molecular Immunology and Embryology, UMR6218, CNRS, Universit Orlans, 3B rue de la Frollerie, Orlans, Cedex 2 45071, France and</json:string></affiliations></json:item><json:item><name>Bernard Ryffel</name><affiliations><json:string>Institut de Transgenose, Molecular Immunology and Embryology, UMR6218, CNRS, Universit Orlans, 3B rue de la Frollerie, Orlans, Cedex 2 45071, France and</json:string></affiliations></json:item><json:item><name>Yann Hrault</name><affiliations><json:string>Institut de Transgenose, Molecular Immunology and Embryology, UMR6218, CNRS, Universit Orlans, 3B rue de la Frollerie, Orlans, Cedex 2 45071, France and</json:string><json:string>E-mail: herault@cnrs-orleans.fr</json:string></affiliations></json:item></author><subject><json:item><lang><json:string>eng</json:string></lang><value>ARTICLES</value></json:item></subject><articleId><json:string>ddm152</json:string></articleId><language><json:string>eng</json:string></language><originalGenre><json:string>research-article</json:string></originalGenre><abstract>Monosomy 21 is a rare human disease due to gene dosage errors disturbing a variety of physiological and morphological systems including brain, skeletal, immune and respiratory functions. Most of the human condition corresponds to partial or mosaic monosomy suggesting that Monosomy 21 may be lethal. In order to search for dosage-sensitive genes involved in the human pathology, we generated by chromosomal engineering a monosomic mouse for the Prmt2Col6a1 interval corresponding to the most telomeric part of human chromosome 21. Haploinsufficiency of the 13 genes, located in the 0.5Mb genetic interval and conserved in man and mouse, caused apparently no morphological defect as observed in patients. However, monosomic mice displayed an enhanced inflammatory response after local intranasal lipopolysaccharide administration with enhanced recruitment of neutrophils and secretion of cytokines such as tumor necrosis factor- (TNF-), IL-1, IL-12p70 and IFN- in the lung as well increased TNF- production after systemic administration. Further analysis demonstrates that monosomic macrophages were involved and that a few genes, Prmt2, Pcnt2, Mcm3ap and Lss located in the region were candidate for the inflammatory response. Altogether, these results demonstrate the existence of dosage-sensitive genes in the Prmt2Col6a1 region that control the inflammation and the lung function. Furthermore, they point out that similar partial Monosomies 21 in human might have eluded the diagnosis due to the very specific defects observed in this murine model.</abstract><qualityIndicators><score>7.688</score><pdfVersion>1.2</pdfVersion><pdfPageSize>609.675 x 795.005 pts</pdfPageSize><refBibsNative>false</refBibsNative><keywordCount>1</keywordCount><abstractCharCount>1551</abstractCharCount><pdfWordCount>8994</pdfWordCount><pdfCharCount>55072</pdfCharCount><pdfPageCount>13</pdfPageCount><abstractWordCount>224</abstractWordCount></qualityIndicators><title>Modeling the monosomy for the telomeric part of human chromosome 21 reveals haploinsufficient genes modulating the inflammatory and airway responses</title><genre><json:string>research-article</json:string></genre><host><volume>16</volume><publisherId><json:string>hmg</json:string></publisherId><pages><last>2052</last><first>2040</first></pages><issn><json:string>0964-6906</json:string></issn><issue>17</issue><genre><json:string>journal</json:string></genre><language><json:string>unknown</json:string></language><eissn><json:string>1460-2083</json:string></eissn><title>Human Molecular Genetics</title></host><categories><wos><json:string>BIOCHEMISTRY & MOLECULAR BIOLOGY</json:string><json:string>GENETICS & HEREDITY</json:string></wos></categories><publicationDate>2007</publicationDate><copyrightDate>2007</copyrightDate><doi><json:string>10.1093/hmg/ddm152</json:string></doi><id>8F88D4D15114343F11E092A217F647CD4526280A</id><score>0.23341109</score><fulltext><json:item><original>true</original><mimetype>application/pdf</mimetype><extension>pdf</extension><uri>https://api.istex.fr/document/8F88D4D15114343F11E092A217F647CD4526280A/fulltext/pdf</uri></json:item><json:item><original>false</original><mimetype>application/zip</mimetype><extension>zip</extension><uri>https://api.istex.fr/document/8F88D4D15114343F11E092A217F647CD4526280A/fulltext/zip</uri></json:item><istex:fulltextTEI uri="https://api.istex.fr/document/8F88D4D15114343F11E092A217F647CD4526280A/fulltext/tei"><teiHeader><fileDesc><titleStmt><title level="a">Modeling the monosomy for the telomeric part of human chromosome 21 reveals haploinsufficient genes modulating the inflammatory and airway responses</title><respStmt><resp>Références bibliographiques récupérées via GROBID</resp><name resp="ISTEX-API">ISTEX-API (INIST-CNRS)</name></respStmt></titleStmt><publicationStmt><authority>ISTEX</authority><publisher>Oxford University Press</publisher><availability><p>2007 The Author(s)</p></availability><date>2007-06-25</date></publicationStmt><sourceDesc><biblStruct type="inbook"><analytic><title level="a">Modeling the monosomy for the telomeric part of human chromosome 21 reveals haploinsufficient genes modulating the inflammatory and airway responses</title><author xml:id="author-1"><persName><forename type="first">Vanessa</forename><surname>Besson</surname></persName><affiliation>Institut de Transgenose, Molecular Immunology and Embryology, UMR6218, CNRS, Universit Orlans, 3B rue de la Frollerie, Orlans, Cedex 2 45071, France and</affiliation></author><author xml:id="author-2"><persName><forename type="first">Vronique</forename><surname>Brault</surname></persName><affiliation>Institut de Transgenose, Molecular Immunology and Embryology, UMR6218, CNRS, Universit Orlans, 3B rue de la Frollerie, Orlans, Cedex 2 45071, France and</affiliation></author><author xml:id="author-3"><persName><forename type="first">Arnaud</forename><surname>Duchon</surname></persName><affiliation>Institut de Transgenose, Molecular Immunology and Embryology, UMR6218, CNRS, Universit Orlans, 3B rue de la Frollerie, Orlans, Cedex 2 45071, France and</affiliation></author><author xml:id="author-4"><persName><forename type="first">Dieudonn</forename><surname>Togbe</surname></persName><affiliation>Institut de Transgenose, Molecular Immunology and Embryology, UMR6218, CNRS, Universit Orlans, 3B rue de la Frollerie, Orlans, Cedex 2 45071, France and</affiliation></author><author xml:id="author-5"><persName><forename type="first">Jean-Charles</forename><surname>Bizot</surname></persName><affiliation>Key-Obs SA, 45150 Orlans, France</affiliation></author><author xml:id="author-6"><persName><forename type="first">Valrie F.J.</forename><surname>Quesniaux</surname></persName><affiliation>Institut de Transgenose, Molecular Immunology and Embryology, UMR6218, CNRS, Universit Orlans, 3B rue de la Frollerie, Orlans, Cedex 2 45071, France and</affiliation></author><author xml:id="author-7"><persName><forename type="first">Bernard</forename><surname>Ryffel</surname></persName><affiliation>Institut de Transgenose, Molecular Immunology and Embryology, UMR6218, CNRS, Universit Orlans, 3B rue de la Frollerie, Orlans, Cedex 2 45071, France and</affiliation></author><author xml:id="author-8"><persName><forename type="first">Yann</forename><surname>Hrault</surname></persName><email>herault@cnrs-orleans.fr</email><affiliation>Institut de Transgenose, Molecular Immunology and Embryology, UMR6218, CNRS, Universit Orlans, 3B rue de la Frollerie, Orlans, Cedex 2 45071, France and</affiliation></author></analytic><monogr><title level="j">Human Molecular Genetics</title><idno type="pISSN">0964-6906</idno><idno type="eISSN">1460-2083</idno><imprint><publisher>Oxford University Press</publisher><date type="published" when="2007-09-01"></date><biblScope unit="volume">16</biblScope><biblScope unit="issue">17</biblScope><biblScope unit="page" from="2040">2040</biblScope><biblScope unit="page" to="2052">2052</biblScope></imprint></monogr><idno type="istex">8F88D4D15114343F11E092A217F647CD4526280A</idno><idno type="DOI">10.1093/hmg/ddm152</idno><idno type="ArticleID">ddm152</idno></biblStruct></sourceDesc></fileDesc><profileDesc><creation><date>2007-06-25</date></creation><langUsage><language ident="en">en</language></langUsage><abstract><p>Monosomy 21 is a rare human disease due to gene dosage errors disturbing a variety of physiological and morphological systems including brain, skeletal, immune and respiratory functions. Most of the human condition corresponds to partial or mosaic monosomy suggesting that Monosomy 21 may be lethal. In order to search for dosage-sensitive genes involved in the human pathology, we generated by chromosomal engineering a monosomic mouse for the Prmt2Col6a1 interval corresponding to the most telomeric part of human chromosome 21. Haploinsufficiency of the 13 genes, located in the 0.5Mb genetic interval and conserved in man and mouse, caused apparently no morphological defect as observed in patients. However, monosomic mice displayed an enhanced inflammatory response after local intranasal lipopolysaccharide administration with enhanced recruitment of neutrophils and secretion of cytokines such as tumor necrosis factor- (TNF-), IL-1, IL-12p70 and IFN- in the lung as well increased TNF- production after systemic administration. Further analysis demonstrates that monosomic macrophages were involved and that a few genes, Prmt2, Pcnt2, Mcm3ap and Lss located in the region were candidate for the inflammatory response. Altogether, these results demonstrate the existence of dosage-sensitive genes in the Prmt2Col6a1 region that control the inflammation and the lung function. Furthermore, they point out that similar partial Monosomies 21 in human might have eluded the diagnosis due to the very specific defects observed in this murine model.</p></abstract><textClass><keywords scheme="keyword"><list><item><term>ARTICLES</term></item></list></keywords></textClass></profileDesc><revisionDesc><change when="2007-06-25">Created</change><change when="2007-09-01">Published</change><change xml:id="refBibs-istex" who="#ISTEX-API" when="2016-10-14">References added</change></revisionDesc></teiHeader></istex:fulltextTEI><json:item><original>false</original><mimetype>text/plain</mimetype><extension>txt</extension><uri>https://api.istex.fr/document/8F88D4D15114343F11E092A217F647CD4526280A/fulltext/txt</uri></json:item></fulltext><metadata><istex:metadataXml wicri:clean="corpus oup" wicri:toSee="no header"><istex:xmlDeclaration>version="1.0" encoding="utf-8"</istex:xmlDeclaration><istex:docType PUBLIC="-//NLM//DTD Journal Publishing DTD v2.3 20070202//EN" URI="journalpublishing.dtd" name="istex:docType"></istex:docType><istex:document><article article-type="research-article"><front><journal-meta><journal-id journal-id-type="publisher-id">hmg</journal-id><journal-id journal-id-type="hwp">hmg</journal-id><journal-title>Human Molecular Genetics</journal-title><issn pub-type="ppub">0964-6906</issn><issn pub-type="epub">1460-2083</issn><publisher><publisher-name>Oxford University Press</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.1093/hmg/ddm152</article-id><article-id pub-id-type="publisher-id">ddm152</article-id><article-categories><subj-group><subject>ARTICLES</subject></subj-group></article-categories><title-group><article-title>Modeling the monosomy for the telomeric part of human chromosome 21 reveals haploinsufficient genes modulating the inflammatory and airway responses</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Besson</surname><given-names>Vanessa</given-names></name><xref ref-type="aff" rid="af1">1</xref></contrib><contrib contrib-type="author"><name><surname>Brault</surname><given-names>Véronique</given-names></name><xref ref-type="aff" rid="af1">1</xref></contrib><contrib contrib-type="author"><name><surname>Duchon</surname><given-names>Arnaud</given-names></name><xref ref-type="aff" rid="af1">1</xref></contrib><contrib contrib-type="author"><name><surname>Togbe</surname><given-names>Dieudonné</given-names></name><xref ref-type="aff" rid="af1">1</xref></contrib><contrib contrib-type="author"><name><surname>Bizot</surname><given-names>Jean-Charles</given-names></name><xref ref-type="aff" rid="af2">2</xref></contrib><contrib contrib-type="author"><name><surname>Quesniaux</surname><given-names>Valérie F.J.</given-names></name><xref ref-type="aff" rid="af1">1</xref></contrib><contrib contrib-type="author"><name><surname>Ryffel</surname><given-names>Bernard</given-names></name><xref ref-type="aff" rid="af1">1</xref></contrib><contrib contrib-type="author"><name><surname>Hérault</surname><given-names>Yann</given-names></name><xref ref-type="aff" rid="af1">1</xref><xref ref-type="corresp" rid="cor1">*</xref></contrib></contrib-group><aff id="af1"><label>1</label><institution>Institut de Transgenose</institution>, <addr-line>Molecular Immunology and Embryology, UMR6218, CNRS, Université Orléans, 3B rue de la Férollerie, Orléans, Cedex 2 45071</addr-line>, <country>France</country> and</aff><aff id="af2"><label>2</label><institution>Key-Obs SA</institution>, <addr-line>45150 Orléans</addr-line>, <country>France</country></aff><author-notes><corresp id="cor1"><label>*</label>To whom correspondence should be addressed. Tel/Fax: <fax>+33 238257930</fax>; Email: <email>herault@cnrs-orleans.fr</email></corresp></author-notes><pub-date pub-type="ppub"><day>1</day><month>9</month><year>2007</year></pub-date><pub-date pub-type="epub"><day>25</day><month>6</month><year>2007</year></pub-date><volume>16</volume><issue>17</issue><fpage>2040</fpage><lpage>2052</lpage><history><date date-type="received"><day>11</day><month>5</month><year>2007</year></date><date date-type="accepted"><day>14</day><month>6</month><year>2007</year></date></history><copyright-statement>©2007 The Author(s)</copyright-statement><copyright-year>2007</copyright-year><license license-type="creative-commons" xlink:href="http://creativecommons.org/licenses/by-nc/2.0/uk/"><p>This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.</p></license><abstract><p>Monosomy 21 is a rare human disease due to gene dosage errors disturbing a variety of physiological and morphological systems including brain, skeletal, immune and respiratory functions. Most of the human condition corresponds to partial or mosaic monosomy suggesting that Monosomy 21 may be lethal. In order to search for dosage-sensitive genes involved in the human pathology, we generated by chromosomal engineering a monosomic mouse for the <italic>Prmt2–Col6a1</italic> interval corresponding to the most telomeric part of human chromosome 21. Haploinsufficiency of the 13 genes, located in the 0.5 Mb genetic interval and conserved in man and mouse, caused apparently no morphological defect as observed in patients. However, monosomic mice displayed an enhanced inflammatory response after local intranasal lipopolysaccharide administration with enhanced recruitment of neutrophils and secretion of cytokines such as tumor necrosis factor-α (TNF-α), IL-1β, IL-12p70 and IFN-γ in the lung as well increased TNF-α production after systemic administration. Further analysis demonstrates that monosomic macrophages were involved and that a few genes, <italic>Prmt2</italic>, <italic>Pcnt2</italic>, <italic>Mcm3ap</italic> and <italic>Lss</italic> located in the region were candidate for the inflammatory response. Altogether, these results demonstrate the existence of dosage-sensitive genes in the <italic>Prmt2–Col6a1</italic> region that control the inflammation and the lung function. Furthermore, they point out that similar partial Monosomies 21 in human might have eluded the diagnosis due to the very specific defects observed in this murine model.</p></abstract></article-meta></front></article></istex:document></istex:metadataXml><mods version="3.6"><titleInfo><title>Modeling the monosomy for the telomeric part of human chromosome 21 reveals haploinsufficient genes modulating the inflammatory and airway responses</title></titleInfo><titleInfo type="alternative" contentType="CDATA"><title>Modeling the monosomy for the telomeric part of human chromosome 21 reveals haploinsufficient genes modulating the inflammatory and airway responses</title></titleInfo><name type="personal"><namePart type="given">Vanessa</namePart><namePart type="family">Besson</namePart><affiliation>Institut de Transgenose, Molecular Immunology and Embryology, UMR6218, CNRS, Universit Orlans, 3B rue de la Frollerie, Orlans, Cedex 2 45071, France and</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Vronique</namePart><namePart type="family">Brault</namePart><affiliation>Institut de Transgenose, Molecular Immunology and Embryology, UMR6218, CNRS, Universit Orlans, 3B rue de la Frollerie, Orlans, Cedex 2 45071, France and</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Arnaud</namePart><namePart type="family">Duchon</namePart><affiliation>Institut de Transgenose, Molecular Immunology and Embryology, UMR6218, CNRS, Universit Orlans, 3B rue de la Frollerie, Orlans, Cedex 2 45071, France and</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Dieudonn</namePart><namePart type="family">Togbe</namePart><affiliation>Institut de Transgenose, Molecular Immunology and Embryology, UMR6218, CNRS, Universit Orlans, 3B rue de la Frollerie, Orlans, Cedex 2 45071, France and</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Jean-Charles</namePart><namePart type="family">Bizot</namePart><affiliation>Key-Obs SA, 45150 Orlans, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Valrie F.J.</namePart><namePart type="family">Quesniaux</namePart><affiliation>Institut de Transgenose, Molecular Immunology and Embryology, UMR6218, CNRS, Universit Orlans, 3B rue de la Frollerie, Orlans, Cedex 2 45071, France and</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Bernard</namePart><namePart type="family">Ryffel</namePart><affiliation>Institut de Transgenose, Molecular Immunology and Embryology, UMR6218, CNRS, Universit Orlans, 3B rue de la Frollerie, Orlans, Cedex 2 45071, France and</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Yann</namePart><namePart type="family">Hrault</namePart><affiliation>Institut de Transgenose, Molecular Immunology and Embryology, UMR6218, CNRS, Universit Orlans, 3B rue de la Frollerie, Orlans, Cedex 2 45071, France and</affiliation><affiliation>E-mail: herault@cnrs-orleans.fr</affiliation><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="research-article" displayLabel="research-article"></genre><subject><topic>ARTICLES</topic></subject><originInfo><publisher>Oxford University Press</publisher><dateIssued encoding="w3cdtf">2007-09-01</dateIssued><dateCreated encoding="w3cdtf">2007-06-25</dateCreated><copyrightDate encoding="w3cdtf">2007</copyrightDate></originInfo><language><languageTerm type="code" authority="iso639-2b">eng</languageTerm><languageTerm type="code" authority="rfc3066">en</languageTerm></language><physicalDescription><internetMediaType>text/html</internetMediaType></physicalDescription><abstract>Monosomy 21 is a rare human disease due to gene dosage errors disturbing a variety of physiological and morphological systems including brain, skeletal, immune and respiratory functions. Most of the human condition corresponds to partial or mosaic monosomy suggesting that Monosomy 21 may be lethal. In order to search for dosage-sensitive genes involved in the human pathology, we generated by chromosomal engineering a monosomic mouse for the Prmt2Col6a1 interval corresponding to the most telomeric part of human chromosome 21. Haploinsufficiency of the 13 genes, located in the 0.5Mb genetic interval and conserved in man and mouse, caused apparently no morphological defect as observed in patients. However, monosomic mice displayed an enhanced inflammatory response after local intranasal lipopolysaccharide administration with enhanced recruitment of neutrophils and secretion of cytokines such as tumor necrosis factor- (TNF-), IL-1, IL-12p70 and IFN- in the lung as well increased TNF- production after systemic administration. Further analysis demonstrates that monosomic macrophages were involved and that a few genes, Prmt2, Pcnt2, Mcm3ap and Lss located in the region were candidate for the inflammatory response. Altogether, these results demonstrate the existence of dosage-sensitive genes in the Prmt2Col6a1 region that control the inflammation and the lung function. Furthermore, they point out that similar partial Monosomies 21 in human might have eluded the diagnosis due to the very specific defects observed in this murine model.</abstract><relatedItem type="host"><titleInfo><title>Human Molecular Genetics</title></titleInfo><genre type="journal">journal</genre><identifier type="ISSN">0964-6906</identifier><identifier type="eISSN">1460-2083</identifier><identifier type="PublisherID">hmg</identifier><identifier type="PublisherID-hwp">hmg</identifier><part><date>2007</date><detail type="volume"><caption>vol.</caption><number>16</number></detail><detail type="issue"><caption>no.</caption><number>17</number></detail><extent unit="pages"><start>2040</start><end>2052</end></extent></part></relatedItem><identifier type="istex">8F88D4D15114343F11E092A217F647CD4526280A</identifier><identifier type="DOI">10.1093/hmg/ddm152</identifier><identifier type="ArticleID">ddm152</identifier><accessCondition type="use and reproduction" contentType="copyright">2007 The Author(s)</accessCondition><recordInfo><recordContentSource>OUP</recordContentSource></recordInfo></mods></metadata><covers><json:item><original>true</original><mimetype>text/html</mimetype><extension>html</extension><uri>https://api.istex.fr/document/8F88D4D15114343F11E092A217F647CD4526280A/covers/html</uri></json:item><json:item><original>true</original><mimetype>image/tiff</mimetype><extension>tiff</extension><uri>https://api.istex.fr/document/8F88D4D15114343F11E092A217F647CD4526280A/covers/tiff</uri></json:item></covers><annexes><json:item><original>true</original><mimetype>image/jpeg</mimetype><extension>jpeg</extension><uri>https://api.istex.fr/document/8F88D4D15114343F11E092A217F647CD4526280A/annexes/jpeg</uri></json:item><json:item><original>true</original><mimetype>image/gif</mimetype><extension>gif</extension><uri>https://api.istex.fr/document/8F88D4D15114343F11E092A217F647CD4526280A/annexes/gif</uri></json:item></annexes><enrichments><istex:catWosTEI uri="https://api.istex.fr/document/8F88D4D15114343F11E092A217F647CD4526280A/enrichments/catWos"><teiHeader><profileDesc><textClass><classCode scheme="WOS">BIOCHEMISTRY & MOLECULAR BIOLOGY</classCode><classCode scheme="WOS">GENETICS & HEREDITY</classCode></textClass></profileDesc></teiHeader></istex:catWosTEI><json:item><type>refBibs</type><uri>https://api.istex.fr/document/8F88D4D15114343F11E092A217F647CD4526280A/enrichments/refBibs</uri></json:item></enrichments><serie></serie></istex></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Wicri/Belgique/explor/OpenAccessBelV2/Data/Istex/Corpus
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 001321 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Istex/Corpus/biblio.hfd -nk 001321 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Wicri/Belgique
|area= OpenAccessBelV2
|flux= Istex
|étape= Corpus
|type= RBID
|clé= ISTEX:8F88D4D15114343F11E092A217F647CD4526280A
|texte= Modeling the monosomy for the telomeric part of human chromosome 21 reveals haploinsufficient genes modulating the inflammatory and airway responses
}}
| This area was generated with Dilib version V0.6.25. |  |