Effects of plasmid DNA injection on cyclophosphamide-accelerated diabetes in NOD mice.

Abstract:

:Type 1 diabetes results in most cases from the destruction of insulin-secreting beta cells by the immune system. Several immunization methods based on administration of autoantigenic polypeptides such as insulin and glutamic acid decarboxylase (GAD) have been used to prevent autoimmune diabetes in the non-obese diabetic (NOD) mouse. In the work presented here, a gene-based approach was taken for a similar purpose. A plasmid carrying different cDNAs was used to investigate the effects of injecting naked DNA on cyclophosphamide-accelerated diabetes in female NOD mice. Four-week-old animals received intramuscular injections of plasmid DNA encoding either intracellular GAD, a secreted form of GAD, or a secreted form of a soft coral luciferase. Monitoring of glycosuria and hyperglycemia indicated that injection of plasmid DNA encoding secreted GAD and secreted luciferase could prevent and delay diabetes, respectively. In contrast, injection of DNA encoding intracellular GAD did not suppress the disease significantly. Analysis of anti-GAD IgG(1) antibody titers in animal sera indicated that diabetes prevention after injection of GAD-encoding DNA was possibly associated with increased Th2-type activity. These results suggest that cellular localization of GAD is a factor to consider in the design of GAD-based genetic vaccines for the prevention of autoimmune diabetes.

journal_name

DNA Cell Biol

journal_title

DNA and cell biology

authors

Filippova M,Liu J,Escher A

doi

10.1089/104454901300069022

keywords:

subject

Has Abstract

pub_date

2001-03-01 00:00:00

pages

175-81

issue

3

eissn

1044-5498

issn

1557-7430

journal_volume

20

pub_type

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