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首页> 外文期刊>American Journal of Physiology >Diabetes models by screen for hyperglycemia in phenotype-driven ENU mouse mutagenesis projects
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Diabetes models by screen for hyperglycemia in phenotype-driven ENU mouse mutagenesis projects

机译：糖尿病模型通过筛选高血糖在表型驱动的ENU小鼠诱变项目中的高血糖

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First published December 4, 2007; doi:10.1152/ajpendo.00592.2007.-More than 150 million people suffer from diabetes mellitus worldwide, and this number is expected to rise substantially within the next decades. Despite its high prevalence, the pathogenesis of diabetes mellitus is not completely understood. Therefore, appropriate experimental models are essential tools to gain more insight into the genetics and pathogenesis of the disease. Here, we describe the current efforts to establish novel diabetes models derived from unbiased, phenotype-driven, large-scale N-ethyl-iV-nitrosourea (ENU) mouse mutagenesis projects started a decade ago using hyperglycemia as a high-throughput screen parameter. Mouse lines were established according to their hyperglycemia phenotype over several generations, thereby revealing a mutation as cause for the aberrant phenotype. Chromosomal assignment of the causative mutation and subsequent candidate gene analysis led to the detection of the mutations that resulted in novelalleles of genes already known to be involved in glucose homeostasis, like glucoki-nase, insulin 2, and insulin receptor. Additional ENU-induced hyperglycemia lines are under genetic analysis. Improvements in screen for diabetic animals are implemented to detect more subtle phenotypes. Moreover, diet challenge assays are being employed to uncover interactions between genetic and environmental factors in the pathogenesis of diabetes mellitus. The new mouse mutants recovered in phenotype-driven ENU mouse mutagenesis projects complement the available models generated by targeted mutagenesis of candidate genes, all together providing the large resource of models required for a systematic dissection of the pathogenesis of diabetes mellitus.
机译：2007年12月4日第一次出版; DOI：10.1152 / ajpendo.00592.2007.-超过1.5亿人患有全球糖尿病的糖尿病，预计该号码将在未来几十年内大幅上涨。尽管患病率很高，但糖尿病的发病机制尚未完全理解。因此，适当的实验模型是必不可少的工具，以获得更多地洞察遗传和疾病发病机制。在这里，我们描述了使用高血糖作为高吞吐量屏参数的努力建立源自无偏异，表型驱动，大规模的N-乙基-IV-亚硝基脲基脲（ENU）小鼠诱变项目的新型糖尿病模型的努力。在几代内，根据其高血糖表型建立小鼠线，从而揭示异常表型的突变。致病性突变和随后的候选基因分析的染色体分配导致检测导致已知参与葡萄糖稳态的基因的新突变，如血糖喹啉，胰岛素2和胰岛素受体。额外的enu诱导的高血糖系列是遗传分析。实施糖尿病动物筛网的改善以检测更微妙的表型。此外，正在采用饮食挑战测定来揭示遗传和环境因素之间的相互作用，在糖尿病的发病机制中。在表型驱动的ENU小鼠诱变项目中回收的新的小鼠突变体补充了候选基因的靶向诱变产生的可用模型，所有这些都在一起提供了系统疏松糖尿病发病机制所需的大量模型资源。

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