期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 100, 期 18, 页码 10376-10381出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1834450100
关键词
-
资金
- NIAID NIH HHS [AI39213, U19 AI046374, AI95380, U19 AI050864, AI46374, R01 AI039213, AI50864] Funding Source: Medline
- NIDDK NIH HHS [R01 DK032493, DK50970, DK32493, DK62718, P30 DK57516, R37 DK032493, DK55969, DK32082, R01 DK055969, P30 DK057516, R01 DK062718] Funding Source: Medline
It has been reported that an insulin 2 gene knockout, when bred onto nonobese diabetic (NOD) mice, accelerates diabetes. We produced insulin 1 gene knockout congenic NOD mice. In contrast to insulin 2, diabetes and insulitis were markedly reduced in insulin 1 knockout mice, with decreased and delayed diabetes in heterozygous females and no insulitis and diabetes in most homozygous female mice. Lack of insulitis was found for insulin 1 female homozygous knockout mice at 8,12, and 37 weeks of age. Despite a lack of insuilitis, insulin 1 homozygous knockout mice spontaneously expressed insulin autoantibodies. Administration of insulin peptide B:9-23 of both insulin 1 and 2 to NOD mice induced insulin autoantibodies. Insulin 1 is not the only lymphocytic target of NOD mice. Insulin 1 homozygous knockout islets, when transplanted into recently diabetic wild-type NOD mice, became infiltrated with lymphocytes and only transiently reversed diabetes. These observations indicate that loss of either insulin gene can influence progression to diabetes of NOD mice and suggest that the preproinsulin 1 gene is crucial for the spontaneous development of NOD insulitis and diabetes.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据