A susceptibility allele from a non-diabetes-prone mouse strain accelerates diabetes in NOD congenic mice
A susceptibility allele from a non-diabetes-prone mouse strain accelerates diabetes in NOD congenic mice
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DOI：
10.2337/diabetes.52.1.218
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发表时间：
2003-01-01
期刊：
影响因子：
7.7
通讯作者：
Morahan, G
中科院分区：
文献类型：
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作者：
Brodnicki, TC;Quirk, F;Morahan, G
非肥胖型糖尿病（NOD）小鼠在遗传上易于自发发展为1型糖尿病。连锁分析已经确定了至少19个易感基因座（Idd 1-Idd 19），这些基因座有助于疾病的发病机制，其中淋巴细胞介导了产生胰岛素的β细胞的特异性破坏。有趣的是，非糖尿病小鼠品系已被证明赋予易感性等位基因受影响的后代在NOD异交的一些Idd基因座。特别是，我们注意到，来自NOD和C57 BL/6（B6）小鼠品系的糖尿病回交后代，在13号染色体上包含Idd 14的区间内表现出增加的异源性。这一结果表明，B6小鼠比NOD小鼠在该基因座上具有更多的致糖尿病等位基因。为了证实这一观察结果，产生了NOD同源小鼠品系，其含有覆盖大部分13号染色体的B6衍生间隔。加上NOD基因组中其他地方已经有效的易感等位基因的组合，染色体13 B6衍生的间隔能够增加发展为1型糖尿病的总体风险，这导致与NOD小鼠相比，同源小鼠中1型糖尿病的发病更早和发病率增加。此外，这种B6衍生的间隔，结合NOD遗传背景，能够克服通常抑制NOD小鼠品系中I型糖尿病的环境条件。
The nonobese diabetic (NOD) mouse is genetically predisposed for the spontaneous development of type 1 diabetes. Linkage analyses have identified at least 19 susceptibility loci (Idd1-Idd19) that contribute to disease pathogenesis in which lymphocytes mediate the specific destruction of insulin-producing beta-cells. Interestingly, nondiabetic mouse strains have been shown to confer susceptibility alleles to affected progeny in NOD outcrosses for some of the Idd loci. In particular, we noted that diabetic backcross progeny, derived from NOD and C57BL/6 (B6) mouse strains, demonstrated increased heterozygousity for an interval encompassing Idd14 on chromosome 13. This result suggested that B6 mice harbor a more diabetogenic allele(s) than NOD mice for this locus. To confirm this observation, a NOD congenic mouse strain, containing a B6-derived interval covering the majority of chromosome 13, was generated. Adding to the combination of already potent susceptibility alleles elsewhere in the NOD genome, the chromosome 13 B6-derived interval was able to increase the overall risk of developing type 1 diabetes, which resulted in an earlier onset and increased incidence of type 1 diabetes in congenic mice as compared with NOD mice. Furthermore, this B6-derived interval, in combination with the NOD genetic background, was able to overcome environmental conditions that typically suppressed type I diabetes in the NOD mouse strain.