@article{JordanKruegerWillmesetal.2011, author = {Jordan, Sabine D. and Kr{\"u}ger, Markus and Willmes, Diana M. and Redemann, Nora and Wunderlich, F. Thomas and Br{\"o}nneke, Hella S. and Merkwirth, Carsten and Kashkar, Hamid and Olkkonen, Vesa M. and B{\"o}ttger, Thomas and Braun, Thomas and Seibler, Jost and Br{\"u}ning, Jens C.}, title = {Obesity-induced overexpression of miRNA-143 inhibits insulin-stimulated AKT activation and impairs glucose metabolism}, series = {Nature Cell Biology}, volume = {13}, journal = {Nature Cell Biology}, number = {4}, publisher = {Nature}, address = {New York}, issn = {1465-7392}, doi = {10.1038/ncb2211}, pages = {434 -- 446}, year = {2011}, abstract = {The contribution of altered post-transcriptional gene silencing to the development of insulin resistance and type 2 diabetes mellitus so far remains elusive. Here, we demonstrate that expression of microRNA (miR)-143 and 145 is upregulated in the liver of genetic and dietary mouse models of obesity. Induced transgenic overexpression of miR-143, but not miR-145, impairs insulin-stimulated AKT activation and glucose homeostasis. Conversely, mice deficient for the miR-143-145 cluster are protected from the development of obesity-associated insulin resistance. Quantitative-mass-spectrometry-based analysis of hepatic protein expression in miR-143-overexpressing mice revealed miR-143-dependent downregulation of oxysterol-binding-protein-related protein (ORP) 8. Reduced ORP8 expression in cultured liver cells impairs the ability of insulin to induce AKT activation, revealing an ORP8-dependent mechanism of AKT regulation. Our experiments provide direct evidence that dysregulated post-transcriptional gene silencing contributes to the development of obesity-induced insulin resistance, and characterize the miR-143-ORP8 pathway as a potential target for the treatment of obesity-associated diabetes.}, language = {en} } @incollection{SeiblerSchwenk2010, author = {Seibler, Jost and Schwenk, Frieder}, title = {Transgenic RNAi Applications in the Mouse}, series = {Methods in Enzymology : Guide to Techniques in Mouse Development, Part B: Mouse Molecular Genetics. 2nd Edition}, booktitle = {Methods in Enzymology : Guide to Techniques in Mouse Development, Part B: Mouse Molecular Genetics. 2nd Edition}, publisher = {Elsevier}, address = {Amsterdam}, isbn = {978-0-12-384880-2}, pages = {367 -- 386}, year = {2010}, language = {en} } @article{GlaserLubitzLovelandetal.2009, author = {Glaser, Stefan and Lubitz, Sandra and Loveland, Kate L. and Ohbo, Kazu and Robb, Lorraine and Schwenk, Frieder and Seibler, Jost and Roellig, Daniela and Kranz, Andrea and Anastassiadis, Konstantinos and Stewart, A. Francis}, title = {The histone 3 lysine 4 methyltransferase, Mll2, is only required briefly in development and spermatogenesis}, series = {Epigenetics \& Chromatin}, volume = {2}, journal = {Epigenetics \& Chromatin}, number = {5}, issn = {1756-8935}, doi = {10.1186/1756-8935-2-5}, pages = {1 -- 16}, year = {2009}, language = {en} } @article{KotnikPopovaTodirasetal.2009, author = {Kotnik, Katarina and Popova, Elena and Todiras, Mihail and Mori, Marcelo A. and Alenina, Natalia and Seibler, Jost and Bader, Michael}, title = {Inducible transgenic rat model for diabetes mellitus based on shRNA-mediated gene knockdown}, series = {Plos One}, volume = {4}, journal = {Plos One}, number = {4}, publisher = {Plos}, address = {San Francisco, California, US}, doi = {10.1371/journal.pone.0005124}, pages = {e5124}, year = {2009}, language = {en} } @article{HeroldBrandtSeibleretal.2008, author = {Herold, Marco J. and Brandt, Jens van den and Seibler, Jost and Reichardt, Holger M.}, title = {Inducible and reversible gene silencing by stable integration of an shRNA-encoding lentivirus in transgenic rats}, series = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {105}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, number = {47}, issn = {1091-6490}, doi = {10.1073/pnas.0806213105}, pages = {18507 -- 18512}, year = {2008}, language = {en} } @article{KochWunderlichSeibleretal.2008, author = {Koch, Linda and Wunderlich, F. Thomas and Seibler, Jost and K{\"o}nner, A. Christine and Hampel, Brigitte and Irlenbusch, Sigrid and Brabant, Georg and Kahn, C. Ronald and Schwenk, Frieder and Br{\"u}ning, Jens C.}, title = {Central insulin action regulates peripheral glucose and fat metabolism in mice}, series = {The Journal of Clinical Investigation (JCI)}, volume = {118}, journal = {The Journal of Clinical Investigation (JCI)}, number = {6}, issn = {1558-8238}, doi = {10.1172/JCI31073}, pages = {2132 -- 2147}, year = {2008}, language = {en} } @article{ChristophBahrenbergVryetal.2008, author = {Christoph, Thomas and Bahrenberg, Gregor and Vry, Jean de and Englberger, Werner and Erdmann, Volker A. and Frech, Moritz and K{\"o}gel, Babette and R{\"o}hl, Thomas and Schiene, Klaus and Schr{\"o}der, Wolfgang and Seibler, Jost and Kurreck, Jens}, title = {Investigation of TRPV1 loss-of-function phenotypes in transgenic shRNA expressing and knockout mice}, series = {Molecular and Cellular Neuroscience}, volume = {37}, journal = {Molecular and Cellular Neuroscience}, number = {3}, issn = {1044-7431}, doi = {10.1016/j.mcn.2007.12.006}, pages = {579 -- 589}, year = {2008}, language = {en} } @article{SeiblerKleinriddersKueterLuksetal.2007, author = {Seibler, Jost and Kleinridders, Andre and K{\"u}ter-Luks, Birgit and Niehaves, Sandra and Br{\"u}ning, Jens C. and Schwenk, Frieder}, title = {Reversible gene knockdown in mice using a tight, inducible shRNA expression system}, series = {Nucleic Acids Research}, volume = {35}, journal = {Nucleic Acids Research}, number = {7}, issn = {1362-4962}, doi = {10.1093/nar/gkm122}, pages = {e54}, year = {2007}, language = {en} } @article{ScheerSnaithWolfetal.2013, author = {Scheer, Nico and Snaith, Mike and Wolf, C. Roland and Seibler, Jost}, title = {Generation and utility of genetically humanized mouse models}, series = {Drug Discovery Today}, volume = {Vol 18}, journal = {Drug Discovery Today}, number = {23-24}, publisher = {Elsevier}, address = {Amsterdam}, issn = {1359-6446}, doi = {10.1016/j.drudis.2013.07.007}, pages = {1200 -- 1211}, year = {2013}, language = {en} } @article{BouwmanGuldenHeijdenetal.2013, author = {Bouwman, Peter and Gulden, Hanneke van der and Heijden, Ingrid van der and Drost, Rinske and Klijn, Christiaan N. and Prasetyanti, Pramudita and Pieterse, Mark and Wientjens, Ellen and Seibler, Jost and Hogervorst, Frank B. L. and Jonkers, Jos}, title = {A High-Throughput Functional Complementation Assay for Classification of BRCA1 Missense Variants}, series = {Cancer Discovery}, journal = {Cancer Discovery}, number = {3}, issn = {2159-8290}, doi = {10.1158/2159-8290.CD-13-0094}, pages = {1142 -- 1152}, year = {2013}, language = {en} }