Evaluation of immune suppressive therapy using autoimmune model mouse

罕见病（如自身免疫性疾病）的治疗方案大多基于个人经验，每种治疗缺乏客观评估。这在很大程度上是由于缺乏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的小鼠模型，使用自身抗原敲除小鼠，它不需要对缺陷的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一个评价各种免疫抑制治疗策略的系统。Dsg 3-/-小鼠最初具有129和C57 BL/6小鼠的混合遗传背景，与C57 BL/6和Balb/C小鼠回交10代，以减少每个个体小鼠的免疫应答差异。建立了一个大的小鼠群体，以提供足够数量的模型小鼠用于本试验。考虑皮肤病变数量、体重减轻和片状脱发的客观评分，评估模型小鼠的疾病活动度。我们的系统的有用性得到证实，通过评估一种新的治疗策略，使用抗CD 40 L单克隆抗体。在未来的各种治疗策略将评估与我们的系统使用的模型小鼠

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