Related Experiment Video
Updated: Apr 11, 2026
A Double Humanized BLT-mice Model Featuring a Stable Human-Like Gut Microbiome and Human Immune System
Published on: August 30, 2019
Use of Humanized Mice to Study the Pathogenesis of Autoimmune and Inflammatory Diseases
Iurii Koboziev1, Yava Jones-Hall, John F Valentine
1*Department of Immunology and Molecular Microbiology, Texas Tech University Health Sciences Center, Lubbock, Texas; †Department of Comparative Pathobiology, Purdue University College of Veterinary Medicine, West Lafayette, Indiana; and ‡Department of Internal Medicine, Gastroenterology, Hepatology and Nutrition, University of Utah, Salt Lake City, Utah.
Abstract:
Animal models of disease have been used extensively by the research community for the past several decades to better understand the pathogenesis of different diseases and assess the efficacy and toxicity of different therapeutic agents. Retrospective analyses of numerous preclinical intervention studies using mouse models of acute and chronic inflammatory diseases reveal a generalized failure to translate promising interventions or therapeutics into clinically effective treatments in patients. Although several possible reasons have been suggested to account for this generalized failure to translate therapeutic efficacy from the laboratory bench to the patient's bedside, it is becoming increasingly apparent that the mouse immune system is substantially different from the human. Indeed, it is well known that >80 major differences exist between mouse and human immunology; all of which contribute to significant differences in immune system development, activation, and responses to challenges in innate and adaptive immunity. This inconvenient reality has prompted investigators to attempt to humanize the mouse immune system to address important human-specific questions that are impossible to study in patients. The successful long-term engraftment of human hematolymphoid cells in mice would provide investigators with a relatively inexpensive small animal model to study clinically relevant mechanisms and facilitate the evaluation of human-specific therapies in vivo. The discovery that targeted mutation of the IL-2 receptor common gamma chain in lymphopenic mice allows for the long-term engraftment of functional human immune cells has advanced greatly our ability to humanize the mouse immune system. The objective of this review is to present a brief overview of the recent advances that have been made in the development and use of humanized mice with special emphasis on autoimmune and chronic inflammatory diseases. In addition, we discuss the use of these unique mouse models to define the human-specific immunopathological mechanisms responsible for the induction and perpetuation of chronic gut inflammation.
Insights
Humanized mice, with over 80 immunological differences from humans, are crucial for studying human-specific diseases. These advanced models enable better understanding and treatment of conditions like autoimmune and chronic inflammatory diseases.
Area of Science:
- Immunology
- Translational Medicine
- Preclinical Research
Background:
- Animal models are vital for disease research but often fail to translate to human treatments.
- Significant immunological differences exist between mice and humans (>80), limiting translatability.
- Humanizing mouse models addresses the need for studying human-specific disease mechanisms.
Purpose of the Study:
- To review advances in developing and utilizing humanized mouse models.
- To highlight the application of these models in autoimmune and chronic inflammatory diseases.
- To discuss using humanized mice for defining human-specific immunopathology in chronic gut inflammation.
Main Methods:
- Utilizing lymphopenic mice with targeted mutations (e.g., IL-2 receptor common gamma chain).
- Achieving long-term engraftment of functional human hematolymphoid cells.
- Employing humanized mice to investigate human-specific immune responses in vivo.
Main Results:
- Successful long-term engraftment of human immune cells in mice is achievable.
- Humanized mice provide a cost-effective model for studying human-specific questions.
- These models facilitate the evaluation of human-specific therapies and disease mechanisms.
Conclusions:
- Humanized mouse models represent a significant advancement in preclinical research.
- They are essential for understanding human-specific immunology and disease pathogenesis.
- These models hold promise for developing effective treatments for human diseases, particularly autoimmune and inflammatory conditions.
