Simone Renner
Molecular Animal Breeding and Biotechnology, Germany
Title: Genetically engineered pig models for translational diabetes research
Biography
Biography: Simone Renner
Abstract
For the development and evaluation of novel diagnostic and therapeutic approaches convincing animal models are of essential importance. Rodents are the model of choice for basic biomedical research. However, for the translation into clinical application additional model systems closer to humans are needed. For various reasons the pig seems to be a very suitable model organism: i) as monogastric omnivore it shares many anatomical and physiological similarities with humans, ii) pigs have a favorable reproductive biology, iii) the whole pig genome sequence is available and iv) methods for targeted genetic modification of the pig are well established nowadays. For translational diabetes research we have established different genetically modified pig models. Transgenic pigs expressing a dominant-negative receptor for the incretin hormone Glucose-dependent Insulinotropic Polypeptide (GIP) reveal a reduced incretin effect, reduced glucose tolerance and insulin secretion as well as reduced beta-cell mass and therefore represent important aspects of the prediabetic state. This model was already successfully used for the search of biomarkers during the prediabetic phase and as well as for the characterization of effects of the GLP-1 receptor agonist liraglutide in adolescence. In contrast pigs expressing the mutant insulin C94Y develop hyperglycemia within the first days of life and represent a model for permanent neonatal diabetes. A biobank representing long-standing, poorly controlled diabetes was successfully established in this model. In general these pig models are valuable for numerous applications, e.g. the preclinical evaluation of novel therapeutic approaches, establishment of in vivo imaging techniques, biomarker discovery, regenerative medicine and developmental biology.