GENETIC DISEASE STRATEGY TO DEVELOP ANIMAL MODELS

意义人类遗传性疾病的动物模型至关重要 用于开发治疗方法。可以在小鼠中创建模型，但许多 小鼠和人类之间的差异往往使这种模型 信息量大。 灵长类动物模型对疾病尤其重要 影响生物体的免疫系统或行为，以及 这些疾病的小鼠模型已被证明是不够的。 目的探索人类隐性遗传病的自然动物模型 遗传病 本研究以囊性纤维化为模型， 遗传病 从1300只灵长类动物（约400 来自CRPRC），并使用SSCP扫描突变。 该项目 即使对于罕见的隐性疾病也是可行的，因为疾病频率 百万分之一的载波频率为1/500。 结果40 已经确定了编码变化; 20个改变的氨基酸， 在所有测试过的物种中都是绝对保守的 通过 检查，这些都不会明显地破坏蛋白质，所以 需要进行功能测试。 至少3个候选突变 功能受损。 未来的方向我们将测试更多的灵长类动物， 完善生理检测，并开始培育 候选隐性突变。 关键词囊性纤维化，遗传性 疾病

Significance Animal models of human genetic diseases are essential for developing therapies.Models can be created in mice, but the many differences between mice and humans often renders such models less informative. Primate models are especially important for diseases that affect the organism's immune system or behavior, as well as diseases for which mouse models have proven to be inadequate. Objectives To discover natural animal models of human recessive genetic diseases. In this study, cystic fibrosis is used as the model genetic disease. Genomic DNA was purified from 1300 primates (~400 from CRPRC) and scanned for mutations using SSCP. The project is feasible even for rare recessive diseases, because a disease frequency of 1 per million has a carrier frequency of 1/500. Results Forty coding changes have been identified; 20 alter amino acids that are absolutely conserved across all species tested to date. By inspection, none of these would obviously inactivate the protein, so functional testing is required. At least 3 of the candidate mutations impair function. Future Directions We will test additional primates, refine the physiological assays, and begin breeding carriers of candidate recessive mutations. KEYWORDS cystic fibrosis, genetic disease