Andrikopoulos Sofianos, Massa Christine M, Aston-Mourney Kathryn, Funkat Alexandra, Fam Barbara C, Hull Rebecca L, Kahn Steven E, Proietto Joseph
University of Melbourne, Department of Medicine, Heidelberg Repatriation Hospital, Heidelberg Heights, Victoria 3081, Australia.
J Endocrinol. 2005 Oct;187(1):45-53. doi: 10.1677/joe.1.06333.
The increasing production of genetically-modified mouse models has necessitated studies to determine the inherent physiological characteristics of commonly used mouse strains. In this study we examined insulin secretory function in response to an intravenous bolus of glucose or glucose plus arginine in anesthetized C57BL/6, DBA/2 and 129T2 mice fed either a control or high fat diet for 6 weeks. The results show that 129T2 mice had higher fasting plasma glucose levels and lower fasting plasma insulin levels compared with C57BL/6 and DBA/2 mice regardless of diet. Furthermore, 129T2 mice were glucose intolerant and secreted significantly less insulin in response to glucose and glucose plus arginine irrespective of diet compared with the other two strains of mice. DBA/2 mice hypersecreted insulin in response to glucose and glucose plus arginine compared with C57BL/6 and 129T2 mice. Moreover while first phase insulin secretion was appropriately increased in response to the high fat diet in C57BL/6 and 129T2 mice, this was not the case for DBA/2 mice. Mean islet area was decreased in response to a high fat diet in DBA/2 mice, while there was no dietary effect on the other two strains. This study highlights the inherent genetic differences that exist among seemingly normal strains of mice that are commonly used to make transgenic and knockout mice. Understanding these differences will provide researchers with the information to choose the appropriate genetic background on which to express their particular genetic alteration.
转基因小鼠模型产量的不断增加，使得有必要开展研究来确定常用小鼠品系的固有生理特征。在本研究中，我们检测了麻醉状态下的C57BL/6、DBA/2和129T2小鼠在静脉注射葡萄糖或葡萄糖加精氨酸后，其胰岛素分泌功能的变化情况。这些小鼠被喂食对照饮食或高脂饮食6周。结果显示，无论饮食如何，与C57BL/6和DBA/2小鼠相比，129T2小鼠的空腹血糖水平更高，空腹血浆胰岛素水平更低。此外，与其他两个品系的小鼠相比，无论饮食如何，129T2小鼠对葡萄糖不耐受，对葡萄糖和葡萄糖加精氨酸的反应分泌的胰岛素显著减少。与C57BL/6和129T2小鼠相比，DBA/2小鼠对葡萄糖和葡萄糖加精氨酸的反应胰岛素分泌过多。此外，虽然C57BL/6和129T2小鼠的第一阶段胰岛素分泌因高脂饮食而适当增加，但DBA/2小鼠并非如此。DBA/2小鼠的胰岛平均面积因高脂饮食而减小，而其他两个品系则没有饮食影响。这项研究突出了常用的用于制作转基因和基因敲除小鼠的看似正常的小鼠品系之间存在的固有遗传差异。了解这些差异将为研究人员提供信息，以便选择合适的遗传背景来表达他们特定的基因改变。
