OVEREXPRESSION OF BETA-2-MICROGLOBULIN IN TRANSGENIC MOUSE ISLET BETA-CELLS RESULTS IN DEFECTIVE INSULIN-SECRETION
- Author(s)
- Allison, J; MALCOLM, L; CULVENOR, J; BARTHOLOMEUSZ, RK; HOLMBERG, K; Miller, JFAP;
- Details
- Publication Year 1991-03,Volume 88,Issue #6,Page 2070-2074
- Journal Title
- PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
- Publication Type
- Journal Article
- Abstract
- Overexpression of heavy chains of the class I major histocompatibility complex in islet beta-cells of transgenic mice is known to induce nonimmune diabetes. We have now overexpressed the secretory protein beta-2-microglobulin in beta-cells. Transgenic mice of one lineage had normal islets. Mice of another lineage did not become overtly diabetic but showed significant depletion of beta-cell insulin. When mice were made homozygous for the transgene locus, they developed diabetes. Introduction of the beta-2-microglobulin chain into class I heavy chain transgenic mice resulted in a significant improvement in their islet morphology and insulin content, and the female mice remained normoglycemic. These results suggest that different transgene molecules overexpressed in beta-cells can cause islet dysfunction, though not necessarily overt diabetes, and that this effect is mediated by the level of transgene expression. Evidence is provided to show that beta-cell disruption by transgene overexpression occurs at the level of protein and involves a defect in insulin secretion.
- Publisher
- NATL ACAD SCIENCES
- Keywords
- CLASS-II MHC; MICE; EXPRESSION; MOLECULES; CLONING; PATHWAY; CHAINS; LY-M11; ATT-20; HEAVY
- Publisher's Version
- https://doi.org/10.1073/pnas.88.6.2070
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 1991-03-01 12:00:00