Links to Exploration step
Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Congenital Asplenia in Mice and Humans with Mutations in a Pbx/Nkx2-5/p15 Module</title>
<author><name sortKey="Koss, Matthew" sort="Koss, Matthew" uniqKey="Koss M" first="Matthew" last="Koss">Matthew Koss</name>
<affiliation><nlm:aff id="A1">Department of Cell & Developmental Biology, Weill Medical College of Cornell University, New York, NY 10065, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Bolze, Alexandre" sort="Bolze, Alexandre" uniqKey="Bolze A" first="Alexandre" last="Bolze">Alexandre Bolze</name>
<affiliation><nlm:aff id="A2">St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY 10065, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Brendolan, Andrea" sort="Brendolan, Andrea" uniqKey="Brendolan A" first="Andrea" last="Brendolan">Andrea Brendolan</name>
<affiliation><nlm:aff id="A1">Department of Cell & Developmental Biology, Weill Medical College of Cornell University, New York, NY 10065, USA</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A3">Laboratory of Lymphoid Organ Development, Fondazione Centro San Raffaele Del Monte Tabor, Milan, Italy, EU</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Saggese, Matilde" sort="Saggese, Matilde" uniqKey="Saggese M" first="Matilde" last="Saggese">Matilde Saggese</name>
<affiliation><nlm:aff id="A1">Department of Cell & Developmental Biology, Weill Medical College of Cornell University, New York, NY 10065, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Capellini, Terence D" sort="Capellini, Terence D" uniqKey="Capellini T" first="Terence D." last="Capellini">Terence D. Capellini</name>
<affiliation><nlm:aff id="A1">Department of Cell & Developmental Biology, Weill Medical College of Cornell University, New York, NY 10065, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Bojilova, Ekaterina" sort="Bojilova, Ekaterina" uniqKey="Bojilova E" first="Ekaterina" last="Bojilova">Ekaterina Bojilova</name>
<affiliation><nlm:aff id="A1">Department of Cell & Developmental Biology, Weill Medical College of Cornell University, New York, NY 10065, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Boisson, Bertrand" sort="Boisson, Bertrand" uniqKey="Boisson B" first="Bertrand" last="Boisson">Bertrand Boisson</name>
<affiliation><nlm:aff id="A2">St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY 10065, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Prall, Owen W J" sort="Prall, Owen W J" uniqKey="Prall O" first="Owen W. J." last="Prall">Owen W. J. Prall</name>
<affiliation><nlm:aff id="A4">The Victor Chang Cardiac Research Institute, Darlinghurst, Australia</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Elliott, David" sort="Elliott, David" uniqKey="Elliott D" first="David" last="Elliott">David Elliott</name>
<affiliation><nlm:aff id="A4">The Victor Chang Cardiac Research Institute, Darlinghurst, Australia</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Solloway, Mark" sort="Solloway, Mark" uniqKey="Solloway M" first="Mark" last="Solloway">Mark Solloway</name>
<affiliation><nlm:aff id="A4">The Victor Chang Cardiac Research Institute, Darlinghurst, Australia</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Lenti, Elisa" sort="Lenti, Elisa" uniqKey="Lenti E" first="Elisa" last="Lenti">Elisa Lenti</name>
<affiliation><nlm:aff id="A3">Laboratory of Lymphoid Organ Development, Fondazione Centro San Raffaele Del Monte Tabor, Milan, Italy, EU</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Hidaka, Chisa" sort="Hidaka, Chisa" uniqKey="Hidaka C" first="Chisa" last="Hidaka">Chisa Hidaka</name>
<affiliation><nlm:aff id="A5">Laboratory for Soft Tissue Research, Hospital of Special Surgery, New York, NY 10021, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Chang, Ching Pin" sort="Chang, Ching Pin" uniqKey="Chang C" first="Ching-Pin" last="Chang">Ching-Pin Chang</name>
<affiliation><nlm:aff id="A6">Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Mahlaoui, Nizar" sort="Mahlaoui, Nizar" uniqKey="Mahlaoui N" first="Nizar" last="Mahlaoui">Nizar Mahlaoui</name>
<affiliation><nlm:aff id="A7">Pediatric Hematology-Immunology Unit, Necker Hospital, AP-HP, Paris 75015, France, EU</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Harvey, Richard P" sort="Harvey, Richard P" uniqKey="Harvey R" first="Richard P." last="Harvey">Richard P. Harvey</name>
<affiliation><nlm:aff id="A4">The Victor Chang Cardiac Research Institute, Darlinghurst, Australia</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A8">Faculty of Medicine, University of New South Wales, Kensington, Australia</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Casanova, Jean Laurent" sort="Casanova, Jean Laurent" uniqKey="Casanova J" first="Jean-Laurent" last="Casanova">Jean-Laurent Casanova</name>
<affiliation><nlm:aff id="A2">St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY 10065, USA</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A7">Pediatric Hematology-Immunology Unit, Necker Hospital, AP-HP, Paris 75015, France, EU</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A9">University Paris Descartes, Paris 75015, France, EU</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A10">Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Necker Medical School, Institut National de la Santé et de la Recherche Médicale, U980, Paris 75015, France, EU</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Selleri, Licia" sort="Selleri, Licia" uniqKey="Selleri L" first="Licia" last="Selleri">Licia Selleri</name>
<affiliation><nlm:aff id="A1">Department of Cell & Developmental Biology, Weill Medical College of Cornell University, New York, NY 10065, USA</nlm:aff>
</affiliation>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">PMC</idno>
<idno type="pmid">22560297</idno>
<idno type="pmc">3356505</idno>
<idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3356505</idno>
<idno type="RBID">PMC:3356505</idno>
<idno type="doi">10.1016/j.devcel.2012.02.009</idno>
<date when="2012">2012</date>
<idno type="wicri:Area/Pmc/Corpus">001D93</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">001D93</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Congenital Asplenia in Mice and Humans with Mutations in a Pbx/Nkx2-5/p15 Module</title>
<author><name sortKey="Koss, Matthew" sort="Koss, Matthew" uniqKey="Koss M" first="Matthew" last="Koss">Matthew Koss</name>
<affiliation><nlm:aff id="A1">Department of Cell & Developmental Biology, Weill Medical College of Cornell University, New York, NY 10065, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Bolze, Alexandre" sort="Bolze, Alexandre" uniqKey="Bolze A" first="Alexandre" last="Bolze">Alexandre Bolze</name>
<affiliation><nlm:aff id="A2">St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY 10065, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Brendolan, Andrea" sort="Brendolan, Andrea" uniqKey="Brendolan A" first="Andrea" last="Brendolan">Andrea Brendolan</name>
<affiliation><nlm:aff id="A1">Department of Cell & Developmental Biology, Weill Medical College of Cornell University, New York, NY 10065, USA</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A3">Laboratory of Lymphoid Organ Development, Fondazione Centro San Raffaele Del Monte Tabor, Milan, Italy, EU</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Saggese, Matilde" sort="Saggese, Matilde" uniqKey="Saggese M" first="Matilde" last="Saggese">Matilde Saggese</name>
<affiliation><nlm:aff id="A1">Department of Cell & Developmental Biology, Weill Medical College of Cornell University, New York, NY 10065, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Capellini, Terence D" sort="Capellini, Terence D" uniqKey="Capellini T" first="Terence D." last="Capellini">Terence D. Capellini</name>
<affiliation><nlm:aff id="A1">Department of Cell & Developmental Biology, Weill Medical College of Cornell University, New York, NY 10065, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Bojilova, Ekaterina" sort="Bojilova, Ekaterina" uniqKey="Bojilova E" first="Ekaterina" last="Bojilova">Ekaterina Bojilova</name>
<affiliation><nlm:aff id="A1">Department of Cell & Developmental Biology, Weill Medical College of Cornell University, New York, NY 10065, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Boisson, Bertrand" sort="Boisson, Bertrand" uniqKey="Boisson B" first="Bertrand" last="Boisson">Bertrand Boisson</name>
<affiliation><nlm:aff id="A2">St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY 10065, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Prall, Owen W J" sort="Prall, Owen W J" uniqKey="Prall O" first="Owen W. J." last="Prall">Owen W. J. Prall</name>
<affiliation><nlm:aff id="A4">The Victor Chang Cardiac Research Institute, Darlinghurst, Australia</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Elliott, David" sort="Elliott, David" uniqKey="Elliott D" first="David" last="Elliott">David Elliott</name>
<affiliation><nlm:aff id="A4">The Victor Chang Cardiac Research Institute, Darlinghurst, Australia</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Solloway, Mark" sort="Solloway, Mark" uniqKey="Solloway M" first="Mark" last="Solloway">Mark Solloway</name>
<affiliation><nlm:aff id="A4">The Victor Chang Cardiac Research Institute, Darlinghurst, Australia</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Lenti, Elisa" sort="Lenti, Elisa" uniqKey="Lenti E" first="Elisa" last="Lenti">Elisa Lenti</name>
<affiliation><nlm:aff id="A3">Laboratory of Lymphoid Organ Development, Fondazione Centro San Raffaele Del Monte Tabor, Milan, Italy, EU</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Hidaka, Chisa" sort="Hidaka, Chisa" uniqKey="Hidaka C" first="Chisa" last="Hidaka">Chisa Hidaka</name>
<affiliation><nlm:aff id="A5">Laboratory for Soft Tissue Research, Hospital of Special Surgery, New York, NY 10021, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Chang, Ching Pin" sort="Chang, Ching Pin" uniqKey="Chang C" first="Ching-Pin" last="Chang">Ching-Pin Chang</name>
<affiliation><nlm:aff id="A6">Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Mahlaoui, Nizar" sort="Mahlaoui, Nizar" uniqKey="Mahlaoui N" first="Nizar" last="Mahlaoui">Nizar Mahlaoui</name>
<affiliation><nlm:aff id="A7">Pediatric Hematology-Immunology Unit, Necker Hospital, AP-HP, Paris 75015, France, EU</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Harvey, Richard P" sort="Harvey, Richard P" uniqKey="Harvey R" first="Richard P." last="Harvey">Richard P. Harvey</name>
<affiliation><nlm:aff id="A4">The Victor Chang Cardiac Research Institute, Darlinghurst, Australia</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A8">Faculty of Medicine, University of New South Wales, Kensington, Australia</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Casanova, Jean Laurent" sort="Casanova, Jean Laurent" uniqKey="Casanova J" first="Jean-Laurent" last="Casanova">Jean-Laurent Casanova</name>
<affiliation><nlm:aff id="A2">St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY 10065, USA</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A7">Pediatric Hematology-Immunology Unit, Necker Hospital, AP-HP, Paris 75015, France, EU</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A9">University Paris Descartes, Paris 75015, France, EU</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A10">Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Necker Medical School, Institut National de la Santé et de la Recherche Médicale, U980, Paris 75015, France, EU</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Selleri, Licia" sort="Selleri, Licia" uniqKey="Selleri L" first="Licia" last="Selleri">Licia Selleri</name>
<affiliation><nlm:aff id="A1">Department of Cell & Developmental Biology, Weill Medical College of Cornell University, New York, NY 10065, USA</nlm:aff>
</affiliation>
</author>
</analytic>
<series><title level="j">Developmental Cell</title>
<idno type="ISSN">1534-5807</idno>
<idno type="eISSN">1878-1551</idno>
<imprint><date when="2012">2012</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass></textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en"><title>SUMMARY</title>
<p id="P6">The molecular determinants of spleen organogenesis and the etiology of isolated congenital asplenia (ICA), a life-threatening human condition, are unknown. We previously reported that <italic>Pbx1</italic>
deficiency causes organ growth defects including asplenia. Here, we show that mice with splenic mesenchyme-specific <italic>Pbx1</italic>
inactivation exhibit hyposplenia. Moreover, the loss of Pbx causes down-regulation of <italic>Nkx2-5</italic>
and derepression of <italic>p15Ink4b</italic>
in spleen mesenchymal progenitors, perturbing the cell cycle. Removal of p15Ink4b in <italic>Pbx1</italic>
spleen-specific mutants partially rescues spleen growth. By whole-exome sequencing of a multiplex kindred with ICA, we identify a heterozygous missense mutation (P236H) in <italic>NKX2-5</italic>
showing reduced transactivation <italic>in vitro</italic>
. This study establishes that a Pbx/Nkx2-5/p15 regulatory module is essential for spleen development.</p>
</div>
</front>
</TEI>
<pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<pmc-dir>properties manuscript</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-journal-id">101120028</journal-id>
<journal-id journal-id-type="pubmed-jr-id">22411</journal-id>
<journal-id journal-id-type="nlm-ta">Dev Cell</journal-id>
<journal-id journal-id-type="iso-abbrev">Dev. Cell</journal-id>
<journal-title-group><journal-title>Developmental Cell</journal-title>
</journal-title-group>
<issn pub-type="ppub">1534-5807</issn>
<issn pub-type="epub">1878-1551</issn>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">22560297</article-id>
<article-id pub-id-type="pmc">3356505</article-id>
<article-id pub-id-type="doi">10.1016/j.devcel.2012.02.009</article-id>
<article-id pub-id-type="manuscript">NIHMS361166</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Article</subject>
</subj-group>
</article-categories>
<title-group><article-title>Congenital Asplenia in Mice and Humans with Mutations in a Pbx/Nkx2-5/p15 Module</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Koss</surname>
<given-names>Matthew</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Bolze</surname>
<given-names>Alexandre</given-names>
</name>
<xref ref-type="aff" rid="A2">2</xref>
<xref ref-type="author-notes" rid="FN1">*</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Brendolan</surname>
<given-names>Andrea</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
<xref ref-type="aff" rid="A3">3</xref>
<xref ref-type="author-notes" rid="FN1">*</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Saggese</surname>
<given-names>Matilde</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Capellini</surname>
<given-names>Terence D.</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
<xref ref-type="author-notes" rid="FN3">@</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Bojilova</surname>
<given-names>Ekaterina</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Boisson</surname>
<given-names>Bertrand</given-names>
</name>
<xref ref-type="aff" rid="A2">2</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Prall</surname>
<given-names>Owen W.J.</given-names>
</name>
<xref ref-type="aff" rid="A4">4</xref>
<xref ref-type="author-notes" rid="FN2">^</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Elliott</surname>
<given-names>David</given-names>
</name>
<xref ref-type="aff" rid="A4">4</xref>
<xref ref-type="author-notes" rid="FN4">~</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Solloway</surname>
<given-names>Mark</given-names>
</name>
<xref ref-type="aff" rid="A4">4</xref>
<xref ref-type="author-notes" rid="FN5">&</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Lenti</surname>
<given-names>Elisa</given-names>
</name>
<xref ref-type="aff" rid="A3">3</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Hidaka</surname>
<given-names>Chisa</given-names>
</name>
<xref ref-type="aff" rid="A5">5</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Chang</surname>
<given-names>Ching-Pin</given-names>
</name>
<xref ref-type="aff" rid="A6">6</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Mahlaoui</surname>
<given-names>Nizar</given-names>
</name>
<xref ref-type="aff" rid="A7">7</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Harvey</surname>
<given-names>Richard P.</given-names>
</name>
<xref ref-type="aff" rid="A4">4</xref>
<xref ref-type="aff" rid="A8">8</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Casanova</surname>
<given-names>Jean-Laurent</given-names>
</name>
<xref ref-type="aff" rid="A2">2</xref>
<xref ref-type="aff" rid="A7">7</xref>
<xref ref-type="aff" rid="A9">9</xref>
<xref ref-type="aff" rid="A10">10</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Selleri</surname>
<given-names>Licia</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
<xref ref-type="corresp" rid="cor1">#</xref>
</contrib>
</contrib-group>
<aff id="A1"><label>1</label>
Department of Cell & Developmental Biology, Weill Medical College of Cornell University, New York, NY 10065, USA</aff>
<aff id="A2"><label>2</label>
St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY 10065, USA</aff>
<aff id="A3"><label>3</label>
Laboratory of Lymphoid Organ Development, Fondazione Centro San Raffaele Del Monte Tabor, Milan, Italy, EU</aff>
<aff id="A4"><label>4</label>
The Victor Chang Cardiac Research Institute, Darlinghurst, Australia</aff>
<aff id="A5"><label>5</label>
Laboratory for Soft Tissue Research, Hospital of Special Surgery, New York, NY 10021, USA</aff>
<aff id="A6"><label>6</label>
Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA</aff>
<aff id="A7"><label>7</label>
Pediatric Hematology-Immunology Unit, Necker Hospital, AP-HP, Paris 75015, France, EU</aff>
<aff id="A8"><label>8</label>
Faculty of Medicine, University of New South Wales, Kensington, Australia</aff>
<aff id="A9"><label>9</label>
University Paris Descartes, Paris 75015, France, EU</aff>
<aff id="A10"><label>10</label>
Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Necker Medical School, Institut National de la Santé et de la Recherche Médicale, U980, Paris 75015, France, EU</aff>
<author-notes><corresp id="cor1"><label>#</label>
<bold>Corresponding author:</bold>
<email>lis2008@med.cornell.edu</email>
, Phone: 1-212-746-5009; Fax: 1-212-746-5596</corresp>
<fn id="FN1" fn-type="equal"><label>*</label>
<p id="P1">These authors contributed equally to this work.</p>
</fn>
<fn id="FN2" fn-type="present-address"><label>^</label>
<p id="P2">Current Address: Walter and Eliza Hall Institute, Parkville, Australia.</p>
</fn>
<fn id="FN3" fn-type="present-address"><label>@</label>
<p id="P3">Current Address: Department of Developmental Biology, Stanford University School of Medicine, Stanford, CA 94305, USA.</p>
</fn>
<fn id="FN4" fn-type="present-address"><label>~</label>
<p id="P4">Current Address: Monash Institute for Stem Cells and Immunology, Monash University, Clayton 3800, Australia.</p>
</fn>
<fn id="FN5" fn-type="present-address"><label>&</label>
<p id="P5">Current Address: Department of Molecular Biology, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA.</p>
</fn>
</author-notes>
<pub-date pub-type="nihms-submitted"><day>6</day>
<month>3</month>
<year>2012</year>
</pub-date>
<pub-date pub-type="epub"><day>03</day>
<month>5</month>
<year>2012</year>
</pub-date>
<pub-date pub-type="ppub"><day>15</day>
<month>5</month>
<year>2012</year>
</pub-date>
<pub-date pub-type="pmc-release"><day>15</day>
<month>5</month>
<year>2013</year>
</pub-date>
<volume>22</volume>
<issue>5</issue>
<fpage>913</fpage>
<lpage>926</lpage>
<permissions><copyright-statement>© 2012 Elsevier Inc. All rights reserved.</copyright-statement>
<copyright-year>2012</copyright-year>
</permissions>
<abstract><title>SUMMARY</title>
<p id="P6">The molecular determinants of spleen organogenesis and the etiology of isolated congenital asplenia (ICA), a life-threatening human condition, are unknown. We previously reported that <italic>Pbx1</italic>
deficiency causes organ growth defects including asplenia. Here, we show that mice with splenic mesenchyme-specific <italic>Pbx1</italic>
inactivation exhibit hyposplenia. Moreover, the loss of Pbx causes down-regulation of <italic>Nkx2-5</italic>
and derepression of <italic>p15Ink4b</italic>
in spleen mesenchymal progenitors, perturbing the cell cycle. Removal of p15Ink4b in <italic>Pbx1</italic>
spleen-specific mutants partially rescues spleen growth. By whole-exome sequencing of a multiplex kindred with ICA, we identify a heterozygous missense mutation (P236H) in <italic>NKX2-5</italic>
showing reduced transactivation <italic>in vitro</italic>
. This study establishes that a Pbx/Nkx2-5/p15 regulatory module is essential for spleen development.</p>
</abstract>
<kwd-group><kwd>Spleen</kwd>
<kwd>Organ growth</kwd>
<kwd>Human Isolated Congenital Asplenia</kwd>
<kwd>Cell cycle</kwd>
<kwd>Pbx</kwd>
<kwd>p15Ink4b</kwd>
<kwd>Nkx2-5</kwd>
</kwd-group>
</article-meta>
</front>
</pmc>
</record>
Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Wicri/Asie/explor/AustralieFrV1/Data/Pmc/Corpus
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 001D937 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Pmc/Corpus/biblio.hfd -nk 001D937 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien |wiki= Wicri/Asie |area= AustralieFrV1 |flux= Pmc |étape= Corpus |type= RBID |clé= |texte= }}
![]() | This area was generated with Dilib version V0.6.33. | ![]() |