Development of novel therapeutics for rheumatoid arthritis utilizing the adenosine deaminase inhibitor

我们试图用被认为是最强的关节炎诱导剂的抗II型胶原抗体鸡尾酒，在商品化的腺苷脱氨酶基因敲除小鼠(Adako)上诱导关节炎。然而，令我们惊讶的是，抗体鸡尾酒不仅没有在Adako上引起关节炎，甚至在野生型窝仔上也没有引起关节炎。这种关节炎诱导的失败被认为是由于这些小鼠的遗传背景造成的。因此，有必要改变小鼠的遗传背景。为了实现这一基因变化，我们一直在进行回交，使这些小鼠对抗体鸡尾酒敏感，这需要所有的3年时间。截至2013年3月，第8代小鼠已经上市，预计这些小鼠具有对抗体鸡尾酒诱导的关节炎敏感的遗传背景。现在是进行关节炎诱导实验的时候了，分析腺苷和腺苷脱氨酶在关节炎症中的作用。

We tried to induce the arthritis on commercially available adenosine deaminase knock-out mice (ADAKO) with the anti-type II collagen antibody cocktail which is considered to be the strongest inducer of arthritis. To our surprise, however, the antibody cocktail failed to induce arthritis not only on ADAKO but even on the wild-type littermates. This failure of the induction of arthritis was considered due to the genetic background of these mice. Thus it was necessary to change the genetic background of the mice. To achieve this genetic change, we have been performing the back-crossing to make these mice susceptible for the antibody cocktail, which needs allthe 3-year period. As of March, 2013, the 8th generation mice are available, thus it is expected that these mice have the genetic background which is sensitive with the arthritis induction by the antibody cocktail. Now it is the time to perform the arthritis induction experiments to dissect the role of adenosine and adenosine deminase on theirroles toward the joint inflammation.