title: Establishment of a human allergy model using human IL-3/GM-CSF-transgenic NOG mice.
abstract: The development of animal models that mimic human allergic responses is crucial to study the pathophysiology of disease and to generate new therapeutic methodologies. Humanized mice reconstituted with human immune systems are essential to study human immune reactions in vivo and are expected to be useful for studying human allergies. However, application of this technology to the study of human allergies has been limited, largely because of the poor development of human myeloid cells, especially granulocytes and mast cells, which are responsible for mediating allergic diseases, in conventional humanized mice. In this study, we developed a novel transgenic (Tg) strain, NOD/Shi-scid-IL2rγ(null) (NOG), bearing human IL-3 and GM-CSF genes (NOG IL-3/GM-Tg). In this strain, a large number of human myeloid cells of various lineages developed after transplantation of human CD34⁺ hematopoietic stem cells. Notably, mature basophils and mast cells expressing FcεRI were markedly increased. These humanized NOG IL-3/GM-Tg mice developed passive cutaneous anaphylaxis reactions when administered anti-4-hydroxy-3-nitrophenylacetyl IgE Abs and 4-hydroxy-3-nitrophenylacetyl. More importantly, a combination of serum from Japanese cedar pollinosis patients and cedar pollen extract also elicited strong passive cutaneous anaphylaxis responses in mice. Thus, to our knowledge, our NOG IL-3/GM-Tg mice are the first humanized mouse model to enable the study of human allergic responses in vivo and are excellent tools for preclinical studies of allergic diseases.
authors: Central Institute for Experimental Animals, Kawasaki-ku, Kawasaki, Kanagawa 210-0821, Japan.
authors: Ryoji
authors: R
authors: Ito
authors: Takeshi
authors: T
authors: Takahashi
authors: Ikumi
authors: I
authors: Katano
authors: Kenji
authors: K
authors: Kawai
authors: Tsutomu
authors: T
authors: Kamisako
authors: Tomoyuki
authors: T
authors: Ogura
authors: Miyuki
authors: M
authors: Ida-Tanaka
authors: Hiroshi
authors: H
authors: Suemizu
authors: Satoshi
authors: S
authors: Nunomura
authors: Chisei
authors: C
authors: Ra
authors: Akio
authors: A
authors: Mori
authors: Sadakazu
authors: S
authors: Aiso
authors: Mamoru
authors: M
authors: Ito
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005434:Flow Cytometry; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000276:immunology*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology*; D007150:Immunohistochemistry; D007377:Interleukin-3 / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic
chemical_list: C508596:IL3 protein, human; D007377:Interleukin-3; D016178:Granulocyte-Macrophage Colony-Stimulating Factor