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Mono(ADP-ribosyl)transferase genes and diabetes in NOD mice. Is there a relationship?
M Cetkovic-Cvrlje1, S D Yang, E H Leiter
1Jackson Laboratory, Bar Harbor, Maine 04609, USA.
Abstract:
The answer to the question posed by the title (is there a relationship between aberrant Art gene expression and IDDM pathogenesis in NOD mice?) remains elusive. Conclusions are currently based almost entirely upon analysis of mRNA transcript levels rather than on T-cell-specific mono-ADP ribosylation activities. Our unpublished data, as well as data published in abstract form by Dr. L. Chatenoud and colleagues (48) indicate that gene transcription is not impaired in splenic leukocytes of older NOD mice, including those with spontaneous IDDM development. Based upon the limited data showing that there may be reduced expression of Art gene products in the earliest T cell immigrants from the NOD thymus, one would have to surmise that If there is a regulatory defect, it may be in allowing single positive thymic T cells to emigrate before they are fully mature. Therefore, development of anti-Art monoclonal antibody together with further studies regarding functions of mono(ADP-ribosyl)transferase in immunoregulation of different subpopulation of T-cells, may finally resolve the role that altered mono(ADP-ribosyl)transferase activities play in the pathogenesis of IDDM in NOD mice.
Insights
The relationship between aberrant Art gene expression and autoimmune diabetes (IDDM) in NOD mice is unclear. Further research into mono(ADP-ribosyl)transferase activities in T-cells is needed to resolve its role in IDDM pathogenesis.
Area of Science:
- Immunology
- Genetics
Background:
- The role of aberrant Art gene expression in the pathogenesis of autoimmune diabetes (IDDM) in Non-Obese Diabetic (NOD) mice is not fully understood.
- Current conclusions rely heavily on mRNA transcript levels, neglecting T-cell-specific mono-ADP ribosylation activities.
Purpose of the Study:
- To investigate the relationship between Art gene expression and IDDM pathogenesis in NOD mice.
- To explore the function of mono(ADP-ribosyl)transferase in T-cell immunoregulation and its potential role in IDDM.
Main Methods:
- Analysis of mRNA transcript levels in splenic leukocytes.
- Investigation of T-cell-specific mono-ADP ribosylation activities.
- Development of anti-Art monoclonal antibody for further studies.
Main Results:
- Gene transcription is not impaired in splenic leukocytes of older NOD mice, even those with spontaneous IDDM.
- Limited data suggests potentially reduced Art gene product expression in early T cell immigrants from the NOD thymus.
Conclusions:
- A potential regulatory defect may involve the premature emigration of single positive thymic T cells before full maturation.
- Further studies on mono(ADP-ribosyl)transferase functions in T-cell subpopulations are crucial to elucidate its role in IDDM pathogenesis in NOD mice.