Bergman M L, Penha-Gonçalves C, Lejon K, Holmberg D
Department of Cell and Molecular Biology, Umeå University, Umeå, Sweden.
Diabetologia. 2001 Aug;44(8):1054-61. doi: 10.1007/s001250100600.
AIMS/HYPOTHESIS: The non-obese diabetic (NOD) mouse spontaneously develops T-cell-dependent autoimmune diabetes. This mouse strain has a number of immune dysfunctions related to T-cell development but so far there are no available data on the proliferation of NOD immature thymocytes. We therefore studied the thymocyte proliferation in the NOD mouse in discrete stages of T-cell development.
We depleted thymocytes in vivo and analysed thymocyte proliferation during the thymus recovery from depletion. We used co-segregation analysis and quantitative loci trait analysis to investigate the genetic control of proliferation impairments in NOD thymocytes.
Immature thymocytes of female NOD mice proliferate with a relatively low rate compared to non-autoimmune C57Bl/6 mice. This aberrant proliferation was most pronounced in CD4-/lo CD8+ cells differentiating from the CD4-CD8- to the CD4+CD8+ stage. A genetic mapping study using an F2 intercross between the NOD and the C57BL/6 strains showed that a major locus controlling this trait is linked to the insulin-dependent diabetes susceptibility locus Idd6.
CONCLUSION/INTERPRETATION: Our results suggest that impairment of proliferation of immature thymocytes is one possible mechanism through which the Idd6 locus contributes to the pathogenesis of diabetes.
目的/假设：非肥胖糖尿病（NOD）小鼠会自发发生T细胞依赖性自身免疫性糖尿病。该小鼠品系存在许多与T细胞发育相关的免疫功能障碍，但目前尚无关于NOD未成熟胸腺细胞增殖的可用数据。因此，我们研究了NOD小鼠在T细胞发育不同阶段的胸腺细胞增殖情况。
我们在体内清除胸腺细胞，并在胸腺从清除状态恢复期间分析胸腺细胞增殖。我们使用共分离分析和数量性状位点分析来研究NOD胸腺细胞增殖受损的遗传控制。
与非自身免疫性C57Bl/6小鼠相比，雌性NOD小鼠的未成熟胸腺细胞增殖率相对较低。这种异常增殖在从CD4-CD8-阶段分化为CD4+CD8+阶段的CD4-/lo CD8+细胞中最为明显。使用NOD和C57BL/6品系之间的F2杂交进行的遗传定位研究表明，控制这一性状的一个主要位点与胰岛素依赖性糖尿病易感位点Idd6相关。
结论/解读：我们的结果表明，未成熟胸腺细胞增殖受损是Idd6位点导致糖尿病发病机制的一种可能机制。
