Schippers Angela, Mateika Silke, Prochnow Blair, Gruber Achim D, Müller Werner, Frischmann Ursula
Department of Experimental Immunology, Helmholtz Centre for Infection Research, Inhoffenstrasse 7, 38124 Braunschweig, Germany.
Mamm Genome. 2008 Apr;19(4):279-91. doi: 10.1007/s00335-008-9105-1. Epub 2008 Apr 5.
EUMORPHIA (European Union Mouse Research for Public Health and Industrial Application) is a research program involved in developing new approaches in phenotyping, mutagenesis, and informatics to improve characterization of mouse models for understanding human physiology and disease. Secondary screen experiments include the development of assays to identify mice with altered susceptibility or resistance to infections. In this context we developed a new model and established a standard operating procedure for the experimental infection of mice with Yersinia (Y.) enterocolitica. In contrast with previous studies that dealt with high-pathogenic Y. enterocolitica, we used the low-pathogenic Y. enterocolitica strain E40 to analyze differences in the immune response of four strains of inbred mice (BALB/c, C3H/HeN, 129P2, C57BL/6) after oral infection. The determination of colony-forming units in Peyer's patches and histologic analysis supported the observations that BALB/c are less able to ameliorate the infection within 21 days. The immune defense of C57BL/6 mice against Yersinia was the most effective resulting in a nearly complete elimination of bacteria after 21 days. C3H/HeN and 129P2 were intermediate. Analysis of serum immunoglobulins (Ig) by Luminex showed a significant increase of IgG2b levels 21 days after infection in all four inbred strains. The other immunoglobulins remained nearly constant. Our infection model discriminates between the efficiency of an infection at an early time point (3 days) and immunity at a later time point (21 days). It is furthermore an appropriate model to characterize genetic differences in resistance and immunity of inbred and mutant mouse lines.
EUMORPHIA(欧盟公共卫生与工业应用小鼠研究)是一个研究项目,致力于在表型分析、诱变和信息学方面开发新方法,以改进小鼠模型的特征描述,从而更好地理解人类生理学和疾病。二级筛选实验包括开发检测方法,以识别对感染易感性或抵抗力发生改变的小鼠。在此背景下,我们开发了一种新模型,并建立了用小肠结肠炎耶尔森菌对小鼠进行实验性感染的标准操作程序。与之前处理高致病性小肠结肠炎耶尔森菌的研究不同,我们使用低致病性小肠结肠炎耶尔森菌菌株E40来分析四种近交系小鼠(BALB/c、C3H/HeN、129P2、C57BL/6)口服感染后免疫反应的差异。对派尔集合淋巴结中菌落形成单位的测定和组织学分析支持了以下观察结果:BALB/c在21天内减轻感染的能力较弱。C57BL/6小鼠对耶尔森菌的免疫防御最为有效,21天后细菌几乎被完全清除。C3H/HeN和129P2处于中间水平。通过Luminex分析血清免疫球蛋白(Ig)发现,感染21天后,所有四种近交系小鼠的IgG2b水平均显著升高。其他免疫球蛋白水平几乎保持不变。我们的感染模型能够区分早期(3天)感染的效率和后期(21天)的免疫情况。此外,它还是一个适用于表征近交系和突变小鼠品系在抵抗力和免疫力方面遗传差异的模型。