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® (JAX) , NOG® (CIEA) mice, or BRG mice, 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.