Transgenic expression of human INS gene in Ins1/Ins2 double knockout mice leads to insulin underproduction and diabetes in some male mice
| Autor: | Danielle Bucchini, Gretta Abou Sleymane, Laëtitia Languille, Loïc Leroux, Alain Ktorza, Susan Saint-Just, Cécile Tourrel-Cuzin, Rajiv L. Joshi, Luciane Lamotte, Melis Karaca, Béatrice Durel |
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| Přispěvatelé: | Laboratoire de physiopathologie de la nutrition (LPN), Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), Douared, Laetitia |
| Rok vydání: | 2006 |
| Předmět: |
Genetically modified mouse
Blood Glucose Male medicine.medical_specialty Transgene medicine.medical_treatment Gene Expression 030209 endocrinology & metabolism Biology Animals Genetically Modified 03 medical and health sciences Diabetes mellitus genetics Mice 0302 clinical medicine Internal medicine Diabetes mellitus Conditional gene knockout Gene expression Glucose Intolerance medicine Diabetes Mellitus Animals Humans Insulin Pancreas 030304 developmental biology 2. Zero hunger 0303 health sciences medicine.disease medicine.anatomical_structure Endocrinology Female |
| Zdroj: | Frontiers in bioscience : a journal and virtual library Frontiers in bioscience : a journal and virtual library, 2007, 12, pp.1586-1593 |
| ISSN: | 1093-9946 |
| Popis: | We have generated transgenic mouse lines expressing exclusively a human INS transgene on an Ins1/Ins2 double knockout (mIKO) background. The transgene expression was driven by either a 4000 bp or a 353 bp promoter. These transgenic lines, designated mIKO:INS4000 and mIKO:INS353, were viable and fertile. Determination of the amounts of insulin transcripts and total pancreatic insulin content revealed relative insulin underproduction in both lines, from birth to adulthood. Total pancreatic insulin stores in mIKO:INS4000 and mIKO:INS353 mice represented only about 50% and 27%, respectively, as compared to wild-type mice. Morphometric analysis of pancreas did not show any compensatory beta-cell hyperplasia. The majority of animals in both lines remained normoglycemic throughout their lives. Nevertheless, glucose tolerance tests revealed glucose intolerance in nearly half of mIKO:INS4000 male mice, likely due to impaired insulin secretion detected in those animals. In addition, a small fraction (2-4%) of male mice in both lines spontaneously developed diabetes with very distinct pathophysiological features. Diabetes was never seen in female animals. The diabetes developed by mIKO:INS353 mice was rapidly lethal, accompanied by a dramatic depletion of pancreatic insulin stores whereas the mIKO:INS4000 diabetic animals could live for several months. This suggests a possible link between the structure of the human INS gene promoter and the type of diabetes developed in these lines. |
| Databáze: | OpenAIRE |
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