Direct transfer of A20 gene into pancreas protected mice from streptozotocin-induced diabetes.
OBJECTIVE
To investigate the efficiency of transfer of A20 gene into pancreas against STZ-induced diabetes.


METHODS
PVP-plasmid mixture was directly transferred into the pancreatic parenchyma 2 d before STZ injection. The uptake of plasmid pcDNA3-LacZ or pcDNA3-A20 was detected by PCR and the expression of LacZ was confirmed by histological analysis with X-gal. A20 expression in the pancreas of pcDNA3-A20 transgenic mice was measured by RT-PCR and Western blots. Urine amylase, NO generation, and histological examination were examined.


RESULTS
Injection of PVP-plasmid mixture directly into the pancreatic parenchyma increased urine amylase concentration 16 h after operation and reversed it to nearly normal 36 h later. On d 33 LacZ expression could be found in spleen, duodenum, and islets. The development of diabetes was prevented by direct A20 gene transferring into the pancreas and A20-mediated protection was correlated with suppression of NO production. The insulitis was ameliorated in A20-treated mice.


CONCLUSIONS
Injection of PVP-plasmid mixture directly into the pancreatic parenchyma led to target gene expression in islets. Direct transfer of A20 gene into the pancreas protected mice from STZ-induced diabetes.
Yu
Lu-Yang
LY
Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Lin
Bo
B
Zhang
Zhen-Lin
ZL
Guo
Li-He
LH
D000681:Amylases / Q000652:urine; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003546:Cysteine Endopeptidases; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000517:prevention & control*; D015870:Gene Expression; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D047908:Intracellular Signaling Peptides and Proteins; D007515:Islets of Langerhans / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic / Q000235:genetics; D009569:Nitric Oxide / Q000378:metabolism*; D009687:Nuclear Proteins; D010179:Pancreas / Q000378:metabolism / Q000473:pathology; D010957:Plasmids; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics / Q000502:physiology; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3; D001616:beta-Galactosidase / Q000096:biosynthesis
D001786:Blood Glucose; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D011506:Proteins; D009569:Nitric Oxide; D000681:Amylases; D001616:beta-Galactosidase; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3; D003546:Cysteine Endopeptidases; C513261:Tnfaip3 protein, mouse