Understanding the function of miRNAs in vivo

Presented by:

Dr. Jost Seibler, Head of Research and Development


The discovery of miRNAs revealed a new level of gene regulation. In addition, several diseases are associated with deregulated miRNA patterns. To understand the physiological relevance of miRNAs, gain or loss of function experiments in vivo are very powerful. Since knockout experiments in mice are well established, the functional analysis of miRNAs has been concentrated on this approach. Techniques allowing the expression of miRNAs in a time-controlled manner in vivo are still lacking. This presentation provides a generally applicable system for temporal control of ubiquitous miRNA expression in mice. A major focus of the webinar will also be on the study of the in vivo function of miR-143 published by the group of Jens Brüning. The authors show that transcription of miR-143 and -145 is upregulated in liver of dietary mouse models of obesity. Induced transgenic overexpression of miR-143, but not of miR-145 causes insulin resistance and impaired insulin stimulated AKT activation. Conversely, mice deficient for the miR-143/145-cluster are protected from the development of obesity-associated insulin resistance. Taconic's approach for the inducible expression of small RNA molecules in mice will enable new insights into miRNA based regulation and molecular disease mechanisms.

Download the presentation slides.
Jordan SD, Krüger M, Willmes DM, Redemann N, Wunderlich FT, Brönneke HS, Merkwirth C, Kashkar H, Olkkonen VM, Böttger T, Braun T, Seibler J, Brüning JC. (2011) Obesity-induced overexpression of miRNA-143 inhibits insulin-stimulated AKT activation and impairs glucose metabolism, Nat Cell Biol, 2011 Apr, 13(4):434-46, Epub 2011 Mar 27

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