In:
The Journal of Immunology, The American Association of Immunologists, Vol. 202, No. 1_Supplement ( 2019-05-01), p. 131.31-131.31
Abstract:
Humanized mice, in which the human hematopoietic system is reconstituted in immunodeficient mice, are a useful animal model to study human hematology and immunology. Although human T or B lymphocytes significantly differentiated in human hematopoietic stem cells (HSC)-transferred humanized mice, myeloid lineage cells, especially granulocytes, do not fully develop in them. In this study, we generated a novel NOG mouse strain, human G-CSF knockin (KI) mouse, to reconstitute mature human neutrophils in their circulation. We constructed the KI vector that the human G-CSF gene is driven by CMV promoter and targeted murine G-CSF receptor locus to exclude the cross reaction to murine G-CSF receptor. Severe murine neutropenia was observed in hG-CSF KI mice due to the dysfunction of murine G-CSF receptor, and the human G-CSF cytokine was extremely produced in their serum. To analyze human hematopoiesis, we transferred human HSC into x-ray irradiated hG-CSF KI mice. During weeks 4–12 of transplantation, human neutrophils and monocytes were significantly developed in hG-CSF KI mice compared to conventional NOG mice. An emergency granulopoiesis was recapitulated in them, since human neutrophils were highly mobilized into PB after zymosan treatment or E. coli infection. In ex-vivo experiments, neutrophils produced ROS after LPS or PMA stimulation, suggesting these neutrophils are functionally matured. This strain is the first humanized mouse that mature human neutrophils developed in PB and is useful to study innate host defense against bacterial infections.
Type of Medium:
Online Resource
ISSN:
0022-1767
,
1550-6606
DOI:
10.4049/jimmunol.202.Supp.131.31
Language:
English
Publisher:
The American Association of Immunologists
Publication Date:
2019
detail.hit.zdb_id:
1475085-5
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