Key Points The NSG/α-Galnull mouse model mimics the human tissues in lacking α-Gal epitopes. Humanized NSG/α-Galnull mice support the development of functional human B cells. Humanized NSG/α-Galnull mice secrete human Abs to α-Gal epitopes. Visual Abstract Mice have been used as accepted tools for investigating complex human diseases and new drug therapies because of their shared genetics and anatomical characteristics with humans. However, the tissues in mice are different from humans in that human cells have a natural mutation in the α1,3 galactosyltransferase (α1,3GT) gene and lack α-Gal epitopes on glycosylated proteins, whereas mice and other nonprimate mammals express this epitope. The lack of α-Gal epitopes in humans results in the loss of immune tolerance to this epitope and production of abundant natural anti-Gal Abs. These natural anti-Gal Abs can be used as an adjuvant to enhance processing of vaccine epitopes to APCs. However, wild-type mice and all existing humanized mouse models cannot be used to test the efficacy of vaccines expressing α-Gal epitopes because they express α-Gal epitopes and lack anti-Gal Abs. Therefore, in an effort to bridge the gap between the mouse models and humans, we developed a new humanized mouse model that mimics humans in that it lacks α-Gal epitopes and secretes human anti-Gal Abs. The new humanized mouse model (Hu-NSG/α-Galnull) is designed to be used for preclinical evaluations of viral and tumor vaccines based on α-Gal epitopes, human-specific immune responses, xenotransplantation studies, and in vivo biomaterials evaluation. To our knowledge, our new Hu-NSG/α-Galnull is the first available humanized mouse model with such features.

中文翻译：

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一种新的人源化小鼠模型模仿人类缺乏 α-Gal 表位并分泌抗-Gal 抗体

关键点 NSG/α-Galnull 小鼠模型模拟缺乏 α-Gal 表位的人体组织。人源化 NSG/α-Galnull 小鼠支持功能性人类 B 细胞的发育。人源化 NSG/α-Galnull 小鼠分泌人类抗体到 α-Gal 表位。视觉抽象小鼠因其与人类共享的遗传学和解剖学特征而被用作研究复杂人类疾病和新药物疗法的公认工具。然而，小鼠的组织与人类的不同之处在于，人类细胞的 α1,3 半乳糖基转移酶 (α1,3GT) 基因具有天然突变，并且糖基化蛋白上缺乏 α-Gal 表位，而小鼠和其他非灵长类哺乳动物表达该表位。人类缺乏 α-Gal 表位会导致对该表位的免疫耐受性丧失，并产生丰富的天然抗-Gal Ab。这些天然抗-Gal Ab 可用作佐剂以增强疫苗表位加工成 APC。然而，野生型小鼠和所有现有的人源化小鼠模型不能用于测试表达 α-Gal 表位的疫苗的功效，因为它们表达 α-Gal 表位并且缺乏抗-Gal 抗体。因此，为了弥合小鼠模型与人类之间的差距，我们开发了一种新的人源化小鼠模型，该模型模仿人类，因为它缺乏 α-Gal 表位并分泌人类抗 Gal Abs。新的人源化小鼠模型 (Hu-NSG/α-Galnull) 旨在用于基于 α-Gal 表位、人类特异性免疫反应、异种移植研究和体内生物材料评估的病毒和肿瘤疫苗的临床前评估。据我们所知，