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Overexpression of Bcl‐2 in T Cells Affects Insulitis in the Nonobese Diabetic Mouse
Author(s) -
Rietz C.,
Screpanti V.,
Brenden N.,
Böhme J.,
Fernández C.
Publication year - 2003
Publication title -
scandinavian journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.934
H-Index - 88
eISSN - 1365-3083
pISSN - 0300-9475
DOI - 10.1046/j.1365-3083.2003.01244.x
Subject(s) - insulitis , nod , nod mice , transgene , biology , enhancer , genetically modified mouse , microbiology and biotechnology , apoptosis , cancer research , immunology , gene , gene expression , genetics
The nonobese diabetic (NOD) mouse is a useful model for human autoimmune diabetes. The gene for the anti‐apoptotic protein Bcl‐2 has previously been suggested as a probable susceptibility candidate for the NOD mouse disease. In this study, we investigated how overexpression of Bcl‐2 in lymphocytes might affect insulitis in NOD mice. A bcl‐2 transgene expressed constitutively under the SV40‐promoter and the 5′Igh enhancer, Eµ, was bred onto NOD background. Two bcl‐2 transgenic NOD strains were produced and analysed, one with overexpression of Bcl‐2 on only B cells and the other with overexpression of Bcl‐2 on both B and T cells. Subsequent to verification of expression pattern and functionality of the transgene, insulitis intensity was investigated in different backcross generations of the two transgenic strains. Overexpression of Bcl‐2 on both B and T cells leads to a statistically significant protection of the mice from insulitis compared with normal littermates. Overexpression of Bcl‐2 on only B cells, on the other hand, does not have any statistically significant effect on insulitis. Possible mechanisms for the effect of Bcl‐2 on insulitis in NOD mice are discussed.