Dominant-Negative Effects of a Novel Mutated Ins2 Allele Causes Early-Onset Diabetes and Severe β-Cell Loss in Munich Ins2C95S Mutant Mice

• DOI: 10.2337/db06-0658
• Publication Date: 2007-04-30T16:48:34Z
• Authors: Nadja Herbach; Birgit Rathkolb; Elisabeth Kemter; Lisa Pichl; Matthias Klaften; Martin Hrabé de ...; Philippe A. Halban; Eckhard Wolf; Bernhard Aigner; Ruediger Wanke
• Keywords: Pancreatic Islets; Wild type; Transversion

The novel diabetic mouse model Munich Ins2C95S was discovered within the N-ethyl-N-nitrosourea mutagenesis screen. These mice exhibit a T→A transversion in insulin 2 (Ins2) gene at nucleotide position 1903 exon 3, which leads to amino acid exchange C95S and loss of A6-A11 intrachain disulfide bond. From 1 month age onwards, blood glucose levels heterozygous mutant were significantly increased compared with controls. fasted postprandial serum mutants indistinguishable from those wild-type littermates. However, after challenge, pancreatic content, homeostasis assessment (HOMA) β-cell indices lower than initial decrease during an tolerance test HOMA resistance higher mice, indicating development mice. total islet volume, volume density β-cells islets, male reduced Electron microscopy showed virtually no secretory granules, endoplasmic reticulum severely enlarged, mitochondria appeared swollen. Thus, are considered valuable study mechanisms dysfunction death diabetes.