Development of autoimmune diabetes in glutamic acid decarboxylase 65 (GAD65) knockout NOD mice

Diabetologia. 2004 Feb;47(2):221-4. doi: 10.1007/s00125-003-1296-0. Epub 2003 Dec 16.


Aims/hypothesis: Type 1 diabetes mellitus, a T-cell-mediated autoimmune disease, results from the selective destruction of insulin-producing pancreatic beta cells. Autoantibodies against beta-cell components are used clinically as sensitive markers of this disease; however, their physiological role has not been clear. To investigate the role of glutamic acid decarboxylase 65 (GAD65) in the development of the Type 1 diabetes of non-obese diabetic (NOD) mice, we analysed and characterised NOD mice with targeted disruption of the GAD65 gene.

Methods: GAD65-deficient mice were previously established. After backcrossing the knockout mutation onto the NOD genetic background for up to eight generations, female littermates of the three resulting genotypes were produced by intercrossing: GAD65 +/+ (n=23), GAD65 +/- (n=62), and GAD65 -/- (n=31).

Results: The cumulative incidence of autoimmune diabetes showed no significant difference among the three groups in longitudinal studies using the Kaplan-Meier method. Islet morphology showed that the progression of islet infiltration did not differ significantly between the three groups.

Conclusion/interpretation: The cumulative incidence of autoimmune diabetes was not influenced by the GAD65 deficiency. These data suggest that GAD65 is not a major regulatory target of beta-cell autoimmunity in NOD mice.

MeSH terms

  • Age Factors
  • Animals
  • Blotting, Northern
  • Codon, Terminator / genetics
  • Diabetes Mellitus, Type 1 / epidemiology
  • Diabetes Mellitus, Type 1 / etiology*
  • Diabetes Mellitus, Type 1 / genetics
  • Disease-Free Survival
  • Female
  • Gene Expression / genetics
  • Glutamate Decarboxylase / genetics
  • Glutamate Decarboxylase / physiology*
  • Glycosuria / epidemiology
  • Glycosuria / etiology
  • Glycosuria / genetics
  • Growth / genetics
  • Heterozygote
  • Homozygote
  • Hybridization, Genetic
  • Inflammation / pathology
  • Islets of Langerhans / pathology
  • Isoenzymes / genetics
  • Isoenzymes / physiology*
  • Male
  • Mice
  • Mice, Inbred NOD
  • Mice, Knockout
  • Mutation / genetics
  • Open Reading Frames / genetics
  • Seizures / genetics


  • Codon, Terminator
  • Isoenzymes
  • Glutamate Decarboxylase
  • glutamate decarboxylase 1
  • glutamate decarboxylase 2