Mice with a human immune system (HIS)

Human immune system (HIS) mice are a specialized type of humanized mouse model created by engrafting human immune cells, tissues, or their precursors (such as hematopoietic stem cells [HSCs]) into immunodeficient mice. These models are typically generated using severely immunodeficient mouse strains, such as NSG, NOG, or BRG, which carry mutations like IL2γgnull combined with Rag gene knockout or SCID mutations on NOD or BALB/c genetic backgrounds. These genetic modifications significantly enhance the engraftment of human cells and improve the ability of the mice to replicate key aspects of the human immune system.

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HIS mouse models are broadly categorized into three types based on the source of human immune cells and the methods used to establish a functional human immune system. Each category has distinct advantages and limitations:

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1. Hu-PBL Mice: Created by transplanting human peripheral blood lymphocytes (PBL) into immunodeficient mice.

2. Hu-HSC Mice: Generated by engrafting human hematopoietic stem cells (HSCs) to reconstitute a human immune system.

3. Hu-BLT Mice: Developed by co-engrafting human fetal liver and thymus tissues along with HSCs, resulting in a more comprehensive human immune system.

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These models are invaluable tools for studying human immune responses, infectious diseases, cancer immunotherapy, and autoimmune disorders in a preclinical setting.