Mapping of murine diabetogenic gene Mody on chromosome 7 at D7Mit258 and its involvement in pancreatic islet and β cell development during the perinatal period
Mapping of murine diabetogenic gene Mody on chromosome 7 at D7Mit258 and its involvement in pancreatic islet and β cell development during the perinatal period
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DOI：
10.1172/jci1842
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发表时间：
1998-05-15
影响因子：
15.9
通讯作者：
Koizumi, A
中科院分区：
文献类型：
--
作者：
Kayo, T;Koizumi, A
小鼠成熟期起病的年轻糖尿病(Mody)基因突变可导致糖尿病，但其纯合性对胰腺的影响尚不清楚。用F1(糖尿病小鼠C57BL6×正常小鼠)杂交获得F2小鼠。大约20%的F2后代在2周龄时患上糖尿病，50%的后代在2周龄时正常，并在5-8周龄期间患糖尿病，其余30%没有糖尿病。对118只2周龄和5-8周龄F2小鼠进行血糖水平的定量性状基因座分析发现，Mody纯合子的胰岛发育不良(与野生型小鼠相似33%)，β细胞密度较低(与野生型小鼠相似20%)，α细胞相对优势(是野生型小鼠的4倍)。电子显微镜观察显示胰岛素分泌颗粒数量明显减少，β细胞密度降低。胰岛素与胰升糖素含量的比值证实了胰岛素含量在第14天的特异性降低：纯合子鼠为0.01，杂合子鼠为0.54，野生型鼠为1.11。这些结果表明，Mody参与了胰岛生长和β细胞功能。
Mutation of the murine maturity-onset diabetes mellitus of the young (Mody) locus induces diabetes, but the effects of its homozygosity on the pancreas remain unknown. F2 mice were obtained by F1 (diabetic C57BL6 x normal Mus mus-culus castaneus) crosses. About 20% of the F2 progeny developed diabetes by 2 wk of age, 50% of the progeny were normal at 2 wk and developed diabetes between 5 and 8 wk of age, and the remaining 30% did not develop diabetes. Quantitative trait locus analysis using blood glucose levels of 118 F2 mice at 2 wk Of age and 5-8 wk of age located Mody within 3 cM of D7Mit258, Histopathological investigation revealed hypoplastic islets (similar to 33% of that of wild-type mice) and a lower density of beta cells (similar to 20% of wild-type) with a reciprocal dominance of alpha cells (four times that of wild-type) in Mody homozygotes. Electron microscopic observations revealed a specific decrease in the number of insulin secretory granules and a lower density of beta cells. Ratios of insulin to glucagon contents confirmed specific decreases in insulin content: 0.01 for homozygotes, 0.54 for heterozygotes, and 1.11 for wild-type mice on day 14. These results suggest that Mody is involved in both islet growth and beta cell function.