Evaluation of immune suppressive therapy using autoimmune model mouse

自身免疫性疾病等罕见疾病的治疗方案大多基于个人经验，每种治疗方案缺乏客观评价。这主要是由于缺乏能很好地模拟相应人类疾病的动物模型。我们最近开发了一种新的活动性疾病小鼠模型，使用自身抗原敲除小鼠，它不需要对缺陷自身抗原的免疫耐受。本研究的目的是利用自身免疫性疾病小鼠模型建立各种免疫抑制治疗策略的评价体系。原具有129和C57BL/6小鼠混合遗传背景的Dsg3 -/-小鼠，经过10代回交与C57BL/6和Balb/C小鼠，以减小个体间免疫应答差异。建立了一个大的小鼠群体，为该实验提供足够数量的模型小鼠。一个客观的评分来评估模型小鼠的疾病活动，考虑皮肤病变的数量，体重减轻和斑驳脱发。通过评估一种使用抗cd40l单克隆抗体的新型治疗策略，我们的系统的实用性得到了证实。在未来，我们的系统将使用模型小鼠来评估各种治疗策略

Treatment regime for rare diseases, such as autoimmune diseases, are mostly based on personal experiences and each treatment lacks objective evaluation. This is largely due to the lack of animal models which well mimic the corresponding human diseases. We have recently developed a novel active disease mouse model using autoantigen knockout mouse, which does not require immune tolerance against the defective autoantigen. The purpose of this study is to develop an evaluation system of various immune suppressive therapeutic strategies using the autoimmune disease mouse model. Dsg3 -/- mice, which originally had a mixed genetic background of 129 and C57BL/6 mouse, were backcrossed to C57BL/6 and Balb/C mouse by 10 generation to reduce the difference of immune response of each individual mouse. A large mouse colony was established to supply a sufficient number of model mice for this assay. An objective score to evaluate the disease activity of the model mouse considering number of skin lesions, weight loss and patchy hair loss. The usefulness of our system was confirmed by evaluating a novel therapeutic strategy using anti-CD40L monoclonal antibody. In the future various therapeutic strategies will be evaluated with our system using the model mouse