| Co-Investigator(Kenkyū-buntansha) |
KATO Ichiro Tohoku University, School of Medicine, Research Associate, 医学部, 助手 (50250741)
YONEKURA Hideto Kanazawa University, School of Medicine, Associate Professor, 医学部, 助教授 (80240373)
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| Budget Amount *help |
¥19,600,000 (Direct Cost: ¥19,600,000)
Fiscal Year 1997: ¥8,600,000 (Direct Cost: ¥8,600,000)
Fiscal Year 1996: ¥11,000,000 (Direct Cost: ¥11,000,000)
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| Research Abstract |
1.To generate mutant mice lacking Reg I gene, the mutated Reg I gene, in which exon 2-3 was replaced by neomycin resistant gene, was electroporated in ES cells, and an ES cell clone mutated the Reg I allele was obtained. A male chimera transmitted the mutant allele to its offspring. Heterogous mice were apparently normal, and gave birth to mice homologous for mutant Reg I locus.
2.Reg I deficient mice showed no morphological changes in various tissues including pancreatic beta cells. Body weight, blood glucose and serum insulin levels in Reg I-deficient mice were almost the same as those in control mice.
3.Aurothioglucose treatment induced obesity with hyperplasia of islet beta-cells in control mice. The islets in aurothioglucose-treated Reg I-deficient mice were significantly smaller than those of control, indicating that islets of Reg I-deficient mice have lower proliferation activity in response to a demand of beta-cell proliferation in adulthood. Therefore, it is quite possible to as
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sume that Reg I-deficient mice easily develop non-insulin dependent diabetes mellitus (NIDDM) when they become obese and be a good model for studying development of NIDDM in obesity.
4.In the ethionine-induced chronic pancreatitis model, Reg I-deficient mice developed severe pancreatitis and the body weight of the mutant mice was lower than that of control mice. This result suggests that Reg I is involved in resistance of chronic pancreatitis and that Reg I-deficient mice is a new model of chronic pancreatitis.
We revealed that all the mouse Reg genes constitute a multigene family, Reg family, which consists of three subtypes (type I,II and III), and that all the Reg genes assigned to the adjacent site of chromosome 6C/D.
6.We examined expression of the other members of Reg family (Reg II,Reg IIIalpha, RegIIIbeta and Reg IIIgamma) in mouse pancreas by Northern blot analyzes, and revealed that expressions of Reg IIIalpha and Reg IIIgamma were increased in Reg I-deficient mice, suggesting a possibility that some functions of Reg I were compensated by the increased expression of remnant Reg family. To clarify this possibility, we are now generating mutant mice deficient in all the Reg family genes. Less
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