Horm Metab Res 1999; 31(5): 340-344
DOI: 10.1055/s-2007-978750
Symposium Reports

© Georg Thieme Verlag Stuttgart · New York

Glutamate Decarboxylase and GABA in Pancreatic Islets: Lessons from Knock-Out Mice

S. F. Kash1 , 2 , B. G. Condie3 , S. Baekkeskov1
  • 1Departments of Medicine and Microbiology/Immunology, and Hormone Research Institute, University of California San Francisco, San Francisco, CA, USA
  • 2Deltagen, Inc., 1031 Bing St., San Carlos, CA 94070, USA
  • 3Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA, USA
Further Information

Publication History

1998

1999

Publication Date:
20 April 2007 (online)

The GABA-synthesizing enzyme glutamic acid decarboxylase (GAD) is expressed in pancreatic β-cells and GABA has been suggested to play a role in islet cell development and function. Mouse β-cells predominantly express the larger isoform of the enzyme, GAD67, and very low levels of the second isoform, GAD65. Yet GAD65 has been shown to be a target of very early autoimmune I-cell responses associated with β-cell destruction in the non-obese diabetic (NOD) mouse model of Type 1 diabetes. Mice deficient in GAD67, GAD65 or both were used to assess whether GABA is important for islet cell development, and whether GAD65 is required for initiation of insulitis and progression to Type 1 diabetes in the mouse. Lack of either GAD65 or GAD67 did not effect the development of islet cells and the general morphology of islets. When GAD65 -/- (129/Sv) mice were backcrossed into the NOD strain for four generations, GAD65-deficient mice developed insulitis similar to GAD65+/+ mice. Furthermore, at the low penetrance of diabetes in this backcross, GAD65-deficient mice developed disease at the same rate and incidence as wildtype mice. The results suggest that GABA generated by either GAD65 or GAD67 is not critically involved in islet formation and that GAD65 expression is not an absolute requirement for development of autoimmune diabetes in the NOD mouse.