<!DOCTYPE art SYSTEM 'http://www.biomedcentral.com/xml/article.dtd'>
<art>
   <ui>2046-2530-1-S1-P102</ui>
   <ji>2046-2530</ji>
   <fm>
      <dochead>Poster presentation</dochead>
      <bibl>
         <title>
            <p>Cellular modelling of Alstr&#246;m syndrome in human primary dermal fibroblasts and derived cells</p>
         </title>
         <aug>
            <au ca="yes" id="A1"><snm>Semple</snm><fnm>RK</fnm><insr iid="I1"/><email>rks16@cam.ac.uk</email></au>
            <au id="A2"><snm>Chen</snm><fnm>J-H</fnm><insr iid="I1"/></au>
            <au id="A3"><snm>Paisey</snm><fnm>RB</fnm><insr iid="I2"/></au>
            <au id="A4"><snm>Barrett</snm><fnm>TG</fnm><insr iid="I3"/></au>
            <au id="A5"><snm>Hales</snm><fnm>M</fnm><insr iid="I4"/></au>
         </aug>
         <insg>
            <ins id="I1"><p>University of Cambridge, UK</p></ins>
            <ins id="I2"><p>Torbay Hospital, UK</p></ins>
            <ins id="I3"><p>Birmingham University, UK</p></ins>
            <ins id="I4"><p>Alstr&#246;m, UK</p></ins>
         </insg>
         <source>Cilia</source>
         
         
         <supplement><title><p>Proceedings of the First International Cilia in Development and Disease Scientific Conference (2012) </p></title><editor>Phil L Beales and Hannah M Mitchison</editor><sponsor><note>This supplement has not been supported by sponsorship or other external funding.</note></sponsor><note>Meeting abstracts</note></supplement><conference><title><p>First International Cilia in Development and Disease Scientific Conference (2012)</p></title><location>London, UK</location><date-range>16-18 May 2012</date-range><url>http://www.ciliopathyalliance.org/</url></conference><issn>2046-2530</issn>
         <pubdate>2012</pubdate>
         <volume>1</volume>
         <issue>Suppl 1</issue>
         <fpage>P102</fpage>
         <url>http://www.ciliajournal.com/content/1/S1/P102</url>
         <xrefbib><pubid idtype="doi">10.1186/2046-2530-1-S1-P102</pubid></xrefbib>
      </bibl>
      <history><pub><date><day>16</day><month>11</month><year>2012</year></date></pub></history>
      <cpyrt><year>2012</year><collab>Semple et al; licensee BioMed Central Ltd.</collab><note>This is an Open Access article distributed under the terms of the Creative Commons Attribution License (<url>http://creativecommons.org/licenses/by/2.0</url>), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</note></cpyrt>
   </fm>
   <bdy>
      <sec>
         <st>
            <p/>
         </st>
         <p>Alstr&#246;m syndrome (AS) is a complex disorder whose manifestations include retinal degeneration, sensorineural hearing loss, cardiomyopathy, liver fibrosis, and severe insulin resistance. It is caused by biallelic loss-of-function mutations in the <it>ALMS1</it> gene, encoding a large centrosomal protein of poorly understood function. Although the syndrome encompasses several cardinal features of ciliopathies, primary cilia have been reported to be morphologically normal in primary cells from patients with AS. In order to dissect out the cellular pathology of AS in humans we have now, in a project led by Alstr&#246;m UK, assembled a bank of dermal fibroblasts from patients with AS. All 11 cell lines studied to date show normal primary cilia on serum starvation. 3/11 lines express near normal levels of ALMS1 protein at the centrosome despite biallelic <it>ALMS1</it> mutations, which will permit refinement of existing genotype-phenotype correlations in AS. We have also generated induced pluripotent stem cells that will be differentiated into cell types relevant to the organ-specific pathologies of AS including cardiomyocytes, hepatocytes and adipocytes. Finally we have used lentivirally-mediated expression of the adipose differentiation regulator PPARgamma2 to reprogramme human dermal fibroblasts to adipocytes. We have developed a highly efficient protocol to produce cells that accumulate triglyceride, show a pattern of gene expression consistent with adipocytes, secrete adiponectin and leptin, and respond physiologically to insulin. Collectively these developments constitute a valuable cellular resource for studying the cellular pathology of AS, and may form the basis of preclinical treatment screens in future.</p>
      </sec>
   </bdy>
</art>