CMV-hFasL transgenic mice are sensitive to low doses of streptozotocin-induced type I diabetes mellitus.
OBJECTIVE
To investigate the role of Fas-FasL pathway in the pathogenesis of streptozotocin (STZ)-induced type I diabetes mellitus.


METHODS
Low dose injections of STZ were used to induce type I diabetes mellitus in the CMV-hFasL transgenic mice. Blood glucose concentration was measured with Glucotrand Plus blood glucose test strips. Expression of hFasL was detected by RT-PCR and Western blotting. The severity of insulitis was determined by histological examination. Expressions of IL-1beta and TNF-alpha mRNA in the pancreas were detected by semi-quantitative RT-PCR analysis. Fas expression in apoptotic RIN-5F cells was also confirmed by RT-PCR in vitro.


RESULTS
hFasL was expressed in the islets of CMV-hFasL transgenic mice. The transgenic mice were sensitive to diabetic induction than the control WT mice. IL-1beta and TNF-alpha expressions in the pancreas of CMV-hFasL transgenic mice were far more than that in WT mice. We also found STZ and IL-1beta could both induce higher expression of Fas in RIN-5F. The combining of Fas-FasL could lead to the apoptosis of beta cells in the CMV-hFasL transgenic mice.


CONCLUSIONS
Fas-FasL interaction plays a significant role in the pathogenic mechanism of type I diabetes mellitus.
Lin
Bo
B
Institute of Biochemistry and Cell Biology, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Zhang
Zhen-Lin
ZL
Yu
Lu-Yang
LY
Guo
Li-He
LH
D000818:Animals; D017209:Apoptosis; D045744:Cell Line, Tumor; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism*; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000378:metabolism*; D053222:Fas Ligand Protein; D020022:Genetic Predisposition to Disease; D007375:Interleukin-1 / Q000096:biosynthesis / Q000235:genetics; D007515:Islets of Langerhans / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D013311:Streptozocin / Q000008:administration & dosage* / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics; D019014:fas Receptor / Q000502:physiology*
D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D007375:Interleukin-1; D008562:Membrane Glycoproteins; D014409:Tumor Necrosis Factor-alpha; D019014:fas Receptor; D013311:Streptozocin