Treatment with GAD65 or BSA does not protect against diabetes in BB rats.
The M(r) 65,000 isoform of glutamic acid decarboxylase (GAD65) has been implicated as the initiating islet cell antigen in the pathogenesis of diabetes, primarily based on studies in non-obese diabetic (NOD) mice. To test the role of this islet cell autoantigen in the pathogenesis of spontaneously occurring diabetes in another animal model, purified recombinant human islet GAD65 was injected i.v. at 200 micrograms/animal into 18-day-old diabetes-prone BB rats. For controls, bovine serum albumin (BSA), which has also been implicated in the pathogenesis of diabetes, or buffer alone was injected into age matched BB rats. At 210 days of age there were no differences in diabetes incidence in the 3 groups, i.e. 73% (11 of 15) in the GAD65-treated, 81% (13 of 16) in the BSA-treated and 65% (11 of 17) in the buffer-treated animals, or in the median age at onset of disease, i.e. 79 days (range 65-111), 87 days (range 60-107) and 86 days (range 74-109), respectively. The lack of protection against diabetes following GAD65 treatment could hypothetically be explained by no or by an aberrant expression of GAD in BB-rat islet cells. However, immunohistochemistry of pancreata and immunoblotting analysis of isolated islets showed that the expression of GAD65 and GAD67 was similar in BB and Lewis rats. In conclusion, these data indicate that neither GAD65 nor BSA autoimmunity is important for the development of diabetes in BB rats, in contrast to the situation in NOD mice, and further emphasizes that extrapolation from only one animal model to autoimmune diabetes in general may not be appropriate.
Petersen
J S
JS
Hagedorn Research Institute, Gentofte, Denmark.
Mackay
P
P
Plesner
A
A
Karlsen
A
A
Gotfredsen
C
C
Verland
S
S
Michelsen
B
B
Dyrberg
T
T
D000818:Animals; D001323:Autoantibodies / Q000032:analysis; D001324:Autoantigens / Q000276:immunology / Q000494:pharmacology*; D002417:Cattle; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology / Q000517:prevention & control*; D005968:Glutamate Decarboxylase / Q000276:immunology / Q000494:pharmacology*; D007108:Immune Tolerance; D007515:Islets of Langerhans / Q000166:cytology / Q000378:metabolism; D011817:Rabbits; D051381:Rats; D011913:Rats, Inbred BB; D012710:Serum Albumin, Bovine / Q000276:immunology / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology
D001323:Autoantibodies; D001324:Autoantigens; D012710:Serum Albumin, Bovine; D005968:Glutamate Decarboxylase