Center for Humanized Mice

描述（由申请人提供）：本提案寻求资金建立人源化小鼠开发中心。内布拉斯加大学医学中心（UNMC）的这个新设施将为转化研究和药物发现提供环境，遗传和异种移植工程小鼠模型，这是UNMC的主流。众所周知，临床研究通常在动物模型中取得成功，但在人类水平上失败。 此外，集中使用微型动物，特别是小鼠，使得对人类的适用性成为问题。反过来，我们正在开发一种资源，将产生改进的动物模型，以研究人类免疫，人类特异性感染，疫苗和人类特异性药物相互作用。预计这些资源将得到有效利用， 新的治疗方法。我们改进现有小鼠品系的目标如下：修改小鼠背景，用于研究对更广泛病原体的类人适应性免疫应答和评价候选疫苗，基于类人糖基化模式创建与人免疫系统功能相容的小鼠品系，修改小鼠背景，用于研究类人药物代谢和药物相互作用，研究HIV-1相关的合并感染，如肝炎、结核病和疟疾，最后检查HIV-1相关的合并症，包括终末器官疾病，如HIV-1相关的神经认知障碍（HAND）。

DESCRIPTION (provided by applicant): This proposal seeks funds to establish a Center for Humanized Mice Development. This new facility at the University of Nebraska Medical Center (UNMC) will offer environmentally, genetically, and xenotransplantation- engineered mouse models for translational studies and drug discovery, which are the mainstream at UNMC. It is well known that often clinical studies are successful in animal models but fail at the human level. Also the focused use of micro-animals, mice in particular, makes applicability to humans problematic. In turn, we are developing a resource that will generate improved animal models to study human immunity, human-specific infections, vaccines, and human-specific drug interactions. The resources are expected to be efficiently utilized for speeding the translation of new therapeutics to patients. Our goals to improve existing strains of mice are as follows: modify mouse backgrounds for the studies of human-like adaptive immune responses to broader range of pathogens and evaluation of vaccine candidates, create strains of mice that are compatible with the function of human immune system based on human-like glycosilation patterns, modify mouse backgrounds for studies of human-like drug metabolism and drug interaction, study HIV-1-related co-infections, such as hepatitis, tuberculosis, and malaria, and lastly examine HIV-1-associated comorbidities, including end-organ diseases like HIV-1-associated neurocognitive disorders (HAND).