TY - JOUR A1 - Raab, Monika A1 - Kappel, Sven A1 - Krämer, Andrea A1 - Sanhaji, Mourad A1 - Matthess, Yves A1 - Kurunci-Csacsko, Elisabeth A1 - Calzada-Wack, Julia A1 - Rathkolb, Birgit A1 - Rosman, Jan A1 - Adler, Thure A1 - Busch, Dirk H. A1 - Esposito, Irene A1 - Fuchs, Helmut A1 - Gailus-Durner, Valérie A1 - Klingenspor, Martin A1 - Wolf, Eckhard A1 - Sänger, Nicole A1 - Prinz, Florian A1 - Hrabe de Angelis, Martin A1 - Seibler, Jost A1 - Yuan, Juping A1 - Bergmann, Martin A1 - Knecht, Rainald A1 - Kreft, Bertolt A1 - Strebhardt, Klaus T1 - Toxicity modelling of Plk1-targeted therapies in genetically engineered mice and cultured primary mammalian cells JF - Nature Communications Y1 - 2011 U6 - http://dx.doi.org/10.1038/ncomms1395 SN - 2041-1723 VL - 2 IS - 395 SP - 1 EP - 11 PB - Nature CY - London ER - TY - JOUR A1 - Hasegawa, Maki A1 - Kapelyukh, Yury A1 - Tahara, Harunobu A1 - Seibler, Jost A1 - Rode, Anja A1 - Krueger, Sylvia A1 - Lee, Dongtao N. A1 - Wolf, C. Roland A1 - Scheer, Nico T1 - Quantitative prediction of human pregnane X receptor and cytochrome P450 3A4 mediated drug-drug interaction in a novel multiple humanized mouse line JF - Molecular Pharmacology Y1 - 2011 U6 - http://dx.doi.org/10.1124/mol.111.071845 SN - 1521-0111 VL - 80 IS - 33 SP - 518 EP - 528 PB - ASPET CY - Bethesda, Md. ER - TY - JOUR A1 - Jordan, Sabine D. A1 - Krüger, Markus A1 - Willmes, Diana M. A1 - Redemann, Nora A1 - Wunderlich, F. Thomas A1 - Brönneke, Hella S. A1 - Merkwirth, Carsten A1 - Kashkar, Hamid A1 - Olkkonen, Vesa M. A1 - Böttger, Thomas A1 - Braun, Thomas A1 - Seibler, Jost A1 - Brüning, Jens C. T1 - Obesity-induced overexpression of miRNA-143 inhibits insulin-stimulated AKT activation and impairs glucose metabolism JF - Nature Cell Biology N2 - 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. Y1 - 2011 U6 - http://dx.doi.org/10.1038/ncb2211 SN - 1465-7392 VL - 13 IS - 4 SP - 434 EP - 446 PB - Nature CY - New York ER - TY - CHAP A1 - Seibler, Jost A1 - Schwenk, Frieder T1 - Transgenic RNAi Applications in the Mouse T2 - Methods in Enzymology : Guide to Techniques in Mouse Development, Part B: Mouse Molecular Genetics. 2nd Edition Y1 - 2010 SN - 978-0-12-384880-2 N1 - Methods in Enzymology : Vol. 477 SP - 367 EP - 386 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Glaser, Stefan A1 - Lubitz, Sandra A1 - Loveland, Kate L. A1 - Ohbo, Kazu A1 - Robb, Lorraine A1 - Schwenk, Frieder A1 - Seibler, Jost A1 - Roellig, Daniela A1 - Kranz, Andrea A1 - Anastassiadis, Konstantinos A1 - Stewart, A. Francis T1 - The histone 3 lysine 4 methyltransferase, Mll2, is only required briefly in development and spermatogenesis JF - Epigenetics & Chromatin Y1 - 2009 U6 - http://dx.doi.org/10.1186/1756-8935-2-5 SN - 1756-8935 VL - 2 IS - 5 SP - 1 EP - 16 ER - TY - JOUR A1 - Kotnik, Katarina A1 - Popova, Elena A1 - Todiras, Mihail A1 - Mori, Marcelo A. A1 - Alenina, Natalia A1 - Seibler, Jost A1 - Bader, Michael T1 - Inducible transgenic rat model for diabetes mellitus based on shRNA-mediated gene knockdown JF - Plos One Y1 - 2009 U6 - http://dx.doi.org/10.1371/journal.pone.0005124 VL - 4 IS - 4 SP - e5124 PB - Plos CY - San Francisco, California, US ER - TY - JOUR A1 - Herold, Marco J. A1 - Brandt, Jens van den A1 - Seibler, Jost A1 - Reichardt, Holger M. T1 - Inducible and reversible gene silencing by stable integration of an shRNA-encoding lentivirus in transgenic rats JF - Proceedings of the National Academy of Sciences of the United States of America Y1 - 2008 U6 - http://dx.doi.org/10.1073/pnas.0806213105 SN - 1091-6490 VL - 105 IS - 47 SP - 18507 EP - 18512 ER - TY - JOUR A1 - Koch, Linda A1 - Wunderlich, F. Thomas A1 - Seibler, Jost A1 - Könner, A. Christine A1 - Hampel, Brigitte A1 - Irlenbusch, Sigrid A1 - Brabant, Georg A1 - Kahn, C. Ronald A1 - Schwenk, Frieder A1 - Brüning, Jens C. T1 - Central insulin action regulates peripheral glucose and fat metabolism in mice JF - The Journal of Clinical Investigation (JCI) Y1 - 2008 U6 - http://dx.doi.org/10.1172/JCI31073 SN - 1558-8238 VL - 118 IS - 6 SP - 2132 EP - 2147 ER - TY - JOUR A1 - Christoph, Thomas A1 - Bahrenberg, Gregor A1 - Vry, Jean de A1 - Englberger, Werner A1 - Erdmann, Volker A. A1 - Frech, Moritz A1 - Kögel, Babette A1 - Röhl, Thomas A1 - Schiene, Klaus A1 - Schröder, Wolfgang A1 - Seibler, Jost A1 - Kurreck, Jens T1 - Investigation of TRPV1 loss-of-function phenotypes in transgenic shRNA expressing and knockout mice JF - Molecular and Cellular Neuroscience Y1 - 2008 U6 - http://dx.doi.org/10.1016/j.mcn.2007.12.006 SN - 1044-7431 VL - 37 IS - 3 SP - 579 EP - 589 ER - TY - JOUR A1 - Seibler, Jost A1 - Kleinridders, Andre A1 - Küter-Luks, Birgit A1 - Niehaves, Sandra A1 - Brüning, Jens C. A1 - Schwenk, Frieder T1 - Reversible gene knockdown in mice using a tight, inducible shRNA expression system JF - Nucleic Acids Research Y1 - 2007 U6 - http://dx.doi.org/10.1093/nar/gkm122 SN - 1362-4962 VL - 35 IS - 7 SP - e54 ER -