Abstract
The prevalence rates of allergic diseases are increasing worldwide, particularly in industrial countries. To date, many mouse models have been generated for allergy research; studies conducted using these models have suggested the importance of cross-talk between immune cells and tissue-resident non-immune cells in the onset of allergic diseases. However, there are several differences between the immune systems of rodents and humans, and human studies are limited. Thus, mice reconstituted with human immune cells are a novel tool for the preclinical evaluation of the efficacy and safety of developing drugs. Genetic technologies for generating humanized mice have improved markedly in recent years. In this review, we will discuss recent progress in allergy research using humanized mice and introduce our recent humanized mouse model of airway inflammation in human immune cells.
Highlights
The development of model animals has greatly contributed to progress in basic research on physiological mechanisms in humans
Human IgE does not induce an immune response via mouse FcεRI in mice, which implies that mouse strains are not suitable for testing human IgE-mediated biological responses such as passive cutaneous anaphylaxis (PCA)
Four strains of second-generation humanized mice were developed (Table 1), including human IL-3, granulocyte macrophage colony stimulating factor (GM-CSF), and stem cell factor (SCF) gene-introduced NSG mice (NSG SGM3), which are characterized by extended myelopoiesis [55,71]
Summary
The development of model animals has greatly contributed to progress in basic research on physiological mechanisms in humans. Because exogenous DNA is integrated into the murine genome, genetic modification techniques including knockout, knockin, and transgenic techniques were initially established using fertilized mouse eggs or embryonic stem cells [1,2,3,4] These techniques enabled the clarification of the physiological functions of numerous genes and generated many important models that mimic the pathogenesis of human diseases. The exocytosis of pre-stored mediators from granulocytes in response to external stimuli, including the cross-linking of Fc receptors, is essential for the development of allergic responses Among these three granulocytes, the eosinophil degranulation response differs markedly between humans and mice. This review focuses on the recent progress in humanized mouse models, including the generation of several strains of second-generation humanized mice and a model for human allergic diseases that was recapitulated using second-generation humanized mice
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