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小鼠6号染色体上的三个基因座影响NOD.C3H同源近交系中I型糖尿病的发病和最终发病率。

Three loci on mouse chromosome 6 influence onset and final incidence of type I diabetes in NOD.C3H congenic strains.

作者信息

Rogner U C, Boitard C, Morin J, Melanitou E, Avner P

机构信息

Génétique Moléculaire Murine CNRS URA 1947, Institut Pasteur, 25 rue du Docteur Roux, Paris Cedex 15, 75724, France.

出版信息

Genomics. 2001 Jun 1;74(2):163-71. doi: 10.1006/geno.2001.6508.

DOI:10.1006/geno.2001.6508
PMID:11386752
Abstract

The development of insulin-dependent diabetes mellitus in both human and mouse is dependent on the interaction between genetic and environmental factors. The analysis of newly created NOD.C3H congenic strains for spontaneous and cyclophosphamide-induced diabetes has allowed the definition of three controlling genetic loci on mouse chromosome 6. A NOD-derived susceptibility allele at the Idd6 locus strongly influences the onset of diabetes in spontaneous diabetes. A NOD-derived resistance allele at the Idd19 locus affects the final diabetes incidence observed in both models, while a novel locus, provisionally termed Idd20, appears to control Idd19 in an epistatic manner. Decreased diabetes incidence is observed in CY-induced diabetes when Idd20 is homozygous for the C3H allele, while heterozygosity is associated with an increase in diabetes incidence. The Idd20, Idd19, and Idd6 candidate regions fall respectively within genetically defined intervals of 4, 7, and 4.5 cM on mouse chromosome 6. From our YAC contig, Idd6 would appear to localize within a ca. 1.5-Mb region on distal chromosome 6.

摘要

人类和小鼠中胰岛素依赖型糖尿病的发展取决于遗传因素和环境因素之间的相互作用。对新创建的NOD.C3H同源近交系进行自发性和环磷酰胺诱导性糖尿病分析,已确定了小鼠6号染色体上的三个控制基因座。Idd6基因座上源自NOD的易感等位基因强烈影响自发性糖尿病中糖尿病的发病。Idd19基因座上源自NOD的抗性等位基因影响两种模型中观察到的最终糖尿病发病率,而一个新基因座(暂称为Idd20)似乎以上位性方式控制Idd19。当Idd20对C3H等位基因纯合时,在环磷酰胺诱导的糖尿病中观察到糖尿病发病率降低,而异合子则与糖尿病发病率增加相关。Idd20、Idd19和Idd6候选区域分别位于小鼠6号染色体上遗传定义的4、7和4.5厘摩区间内。根据我们的酵母人工染色体重叠群,Idd6似乎定位在6号染色体远端约1.5兆碱基的区域内。

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