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Distinct Pattern of GAD65 and GAD67 Gene Expression in the Pancreas of NOD Mouse

Other Title
자가면역 당뇨모델인 NOD mouse의 ontogeny에 따른 GAD 유전자의 특이한 발현양상
고, 인영; 강, 엽
The journal of Korean diabetes association, 21(3):243-253, 1997
Journal Title
The journal of Korean diabetes association; 당뇨병
Background: Glutamic acid decarboxylase(GAD; EC, one of the major β-cell

autoantigens in IDDM, is an enzyme which catalyzes the synthesis of major inhibitory

neurotransmitter, γ-aminobutyric acid(GABA), in the mammalian brain, pancreas and

other organs. Two isoforms of GAD, GAD65 and GAD67, have been identified which differ in their intracellular localization. Autoantibodies to GAD have been detected

several years before the clinical onset of IDDM, implicating GAD as a leading

autoantigen which somehow correlated with the pathogenesis of IDDM. We have

determined the characteristics of GAD isoform expression in the pancreas of NOD

mouse, an animal model extensively employed in IDDM study, using RT-PCR and Southern blot methods.

Methods: Pancreas was obtained from female NOD mouse(neonate, 4, 8, 12, 16, 20

week-old) and age-matched female ICR mouse. Total cellular RNA was isolated by acid

guanidinium thiocyanate method and employed in the RT-PCR amplification using

GAD65- and GAD67-specific primer designed in our laboratory. The PCR product was

blotted onto the nylon membrane and subjected to Southern analysis using

32P-ATP labelled hybridization probe.

Results: In NOD pancreas, GAD67 was expressed six times higher than GAD65 at

neonatal stage. Then, the expression was dramatically decreased from 4 weeks when the

pancreatic insulitis begins to occur. After 12 weeks of age, both GAD67 and GAD65

expression was almost undetectable. However, in control ICR mouse, there were no

significant differences between GAD65 and GAD67 expression throughout the ages. And,

the expression of both GAD65 and GAD67 was not decreased with ages in contrast to

NOD mouse.

Conclusion: In this experiment, we found that the expression of GAD isoforms in

NOD mouse shows distinct pattern in comparison to that of control ICR mouse. The

expression of GAD67 was significantly higher than GAD65 in neonatal NOD mouse while, in control ICR mouse, same level of GAD isoforms expression was observed.

This finding clearly suggested the possibility that the expression of GAD isoforms in diabetic NOD mouse is quite distinct and may somehow play a role in the pathogenesis of diabetes although the precise mechanism remains to be unveiled. In addition, our data also supported the hypothesis that expressional pattern, and, if possible, the etiophysiological function of GAD isoforms in NOD mouse pancreas may be quite different from that in human pancreas.
Insulin-dependent diabetes mellitus(IDDM)non-obese diabetic(NOD) mouseGAD65GAD67RNART-PCRSouthern blotontogenyExpression
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