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Lab. of Animal Res. Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan, Lab. of Mol. Genetics, Institute of Medical Science, Univ. of Tokyo, Tokyo, Japan Humanized mice are useful tools for development of therapeutic drugs. Recently, we established hIL-3/GMCSF (3GM) Tg NOG mice, in which a large number of basophils and mast cells can develop after human HSC transfer and allergic inflammation can be elicited. In this study, we attempted to induce asthmatic airway inflammation by hIL-33 into humanized 3GM Tg mice. The level of hIL-13 in BALF significantly increased in 3GM Tg mice after intratracheal administration of hIL-33. Together with this observation, goblet cell hyperplasia and periostin secretion occurred in lungs of hIL-33-treated 3GM Tg mice. However, these mice failed to recruit human eosinophils into their lung. To address this issue, we newly generated hIL-3/GM/IL-5 (Triple) Tg mice and examined whether eosinophils infiltrate into the airway. We found a significant number of human eosinophils in BALF of Triple Tg mice but not of the other strains. Consistent with this, a significant amount of murine Eotaxin has been detected in Tg mice. These results demonstrate that hIL-3 and hGM-CSF are sufficient to support the differentiation of hIL-13 producing cells, which would include hIL-33 receptor expressing mast cells and basophils, and that hIL-5 and mEotaxin1 may cooperate to induce eosinophil infiltration. This is the first humanized mouse model that fully recapitulated several significant human asthmatic features.

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[Disease Models] [Neuroscience, Behavior] [Genetics, Breeding, Gene Functions, Bio-Resources] [Management, Ethics, Welfare] [International Presentation] [Anatomy, Histology, Pathology] [Reproduction Strain Development] [International Awards] [Microbiology, Infection, Immunity] [Microbiology, Infection, Immunity] [Primates (Methodology, Biochemistry)] [Embryo Manipulation, Regenerative Medicine]