Kachapati Kritika, Adams David, Bednar Kyle, Ridgway William M
Division of Immunology, Allergy, and Rheumatology, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
Methods Mol Biol. 2012;933:3-16. doi: 10.1007/978-1-62703-068-7_1.
The non-obese diabetic (NOD) mouse spontaneously develops type 1 diabetes (T1D) and has thus served as a model for understanding the genetic and immunological basis, and treatment, of T1D. Since its initial description in 1980, however, the field has matured and recognized that prevention of diabetes in NOD mice (i.e., preventing the disease from occurring by an intervention prior to frank diabetes) is relatively easy to achieve and does not correlate well with curing the disease (after the onset of frank hyperglycemia). Hundreds of papers have described the prevention of diabetes in NOD mice but only a handful have described its actual reversal. The paradoxical conclusion is that preventing the disease in NOD mice does not necessarily tell us what caused the disease nor how to reverse it. The NOD mouse model is therefore best used now, with respect to human disease, as a way to understand the genetic and immunologic causes of and as a model for trying to reverse disease once hyperglycemia occurs. We describe how genetic approaches to identifying causative gene variants can be adapted to identify novel therapeutic agents for reversing new-onset T1D.
非肥胖糖尿病（NOD）小鼠会自发发展为1型糖尿病（T1D），因此一直被用作理解T1D的遗传和免疫基础以及治疗方法的模型。然而，自1980年首次描述以来，该领域已经成熟，并认识到在NOD小鼠中预防糖尿病（即通过在明显糖尿病发生之前进行干预来预防疾病）相对容易实现，但与治愈疾病（在明显高血糖发作之后）的相关性并不好。数百篇论文描述了在NOD小鼠中预防糖尿病的方法，但只有少数几篇描述了其实际逆转情况。矛盾的结论是，在NOD小鼠中预防疾病并不一定能告诉我们疾病的病因以及如何逆转它。因此，就人类疾病而言，NOD小鼠模型目前最好用作一种了解遗传和免疫病因的方法，以及在高血糖发生后尝试逆转疾病的模型。我们描述了如何调整用于识别致病基因变异的遗传方法，以识别用于逆转新发T1D的新型治疗药物。
