Center for Humanized Mice

描述(申请人提供)：本提案寻求建立人性化会展发展中心的资金。内布拉斯加州大学医学中心(UNMC)的这个新设施将提供环境、遗传和异种移植工程小鼠模型，用于翻译研究和药物发现，这是UNMC的主流。众所周知，临床研究在动物模型上通常是成功的，但在人类水平上却失败了。 此外，微型动物，特别是小鼠的集中使用，使其对人类的适用性成为问题。反过来，我们正在开发一种资源，该资源将产生改进的动物模型，以研究人类免疫、人类特有的感染、疫苗和人类特有的药物相互作用。预计这些资源将得到有效利用，以加快翻译 为患者提供新的治疗方法。我们改进现有小鼠品系的目标如下：为更广泛的病原体研究和候选疫苗评估修改类人适应性免疫反应的小鼠背景；基于类人糖化模式创建与人类免疫系统功能兼容的小鼠品系；为研究类人药物代谢和药物相互作用修改小鼠背景；研究与HIV-1相关的合并感染，如肝炎、结核病和疟疾；以及最后检查与HIV-1相关的共病，包括像HIV-1相关的神经认知障碍(Hand)等终末期器官疾病。

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).