Division of Medical Inflammation Research, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
Scand J Immunol. 2011 Jan;73(1):46-52. doi: 10.1111/j.1365-3083.2010.02479.x.
The strategy of using heterogeneous stock (HS) mice has proven to be successful in fine mapping of quantitative trait loci in complex diseases. However, whether these mice can be used for arthritis, encephalomyelitis and autoimmune phenotypes has not been addressed. Here, we screened the Northport HS mice for arthritis phenotypes using three different models: collagen-induced arthritis (CIA), using rat, bovine or chicken collagen type II (CII); recombinant human glucose-6-phosphate isomerase (G6PI)-induced arthritis; and collagen antibody-induced arthritis (CAIA). Irrespective of the origin of collagen, we found HS mice to be fairly resistant to CIA and G6PI-induced arthritis, despite the development of antibodies against the respective antigens. On the other hand, HS mice were found to be susceptible for CAIA. Similarly, these mice developed encephalomyelitis (EAE) induced either with mouse or rat spinal cord homogenate (SCH), or with recombinant rat myelin oligodendrocyte glycoprotein, with elevated antibody levels against CNS proteins. Accordingly, we conclude that the use of HS mice for fine mapping and positional cloning of gene(s) involved in CAIA and EAE is possible, but not for collagen- and G6PI-induced arthritis.
利用异质品系（HS）小鼠在复杂疾病的数量性状基因座精细定位中已被证明是成功的策略。然而，这些小鼠是否可用于关节炎、脑脊髓炎和自身免疫表型尚未得到解决。在这里，我们使用三种不同的模型筛选北港 HS 小鼠的关节炎表型：胶原诱导关节炎（CIA），使用大鼠、牛或鸡 II 型胶原（CII）；重组人葡萄糖-6-磷酸异构酶（G6PI）诱导关节炎；以及胶原抗体诱导关节炎（CAIA）。无论胶原的来源如何，我们发现 HS 小鼠对 CIA 和 G6PI 诱导的关节炎相当具有抗性，尽管针对各自抗原产生了抗体。另一方面，HS 小鼠被发现对 CAIA 易感。同样，这些小鼠发展为用小鼠或大鼠脊髓匀浆（SCH）或用重组大鼠髓鞘少突胶质细胞糖蛋白诱导的脑脊髓炎（EAE），并对中枢神经系统蛋白产生升高的抗体水平。因此，我们得出结论，使用 HS 小鼠进行 CAIA 和 EAE 相关基因的精细定位和定位克隆是可能的，但不适用于胶原和 G6PI 诱导的关节炎。
