Development of the next generation humanized mouse for drug discovery

Ito Ryoji

doi:10.1254/fpj.151.160

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Other Title

次世代型ヒト化マウスの開発と創薬研究への応用
創薬シリーズ(8)創薬研究の新潮流(21)次世代型ヒト化マウスの開発と創薬研究への応用
ソウヤクシリーズ(8)ソウヤクケンキュウノシンチョウリュウ(21)ジセダイガタヒトカマウスノカイハツトソウヤクケンキュウエノオウヨウ

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<p>A humanized mouse, which is efficiently engrafted human cells and tissues, is an important tool to mimic human physiology for biomedical researches. Since 2000s, severe combined immunodeficient mouse strains such as NOG, BRG, and NSG mice have been generated. They are great recipients to create humanized mouse models compared to previous other immunodeficient strains due to their multiple dysfunctions of innate and acquired immunity. Especially, the transfer of human hematopoietic stem cells into these immunodeficient mice has been enabled to reconstitute human immune systems, because the mice show high engraftment level of human leukocyte in peripheral blood (～50%), spleen and bone marrow (60～90%) and generate well-differentiated multilineage human immune cells including lymphoid and myeloid lineage cells. Using these mice, several human disease models such as cancer, allergy, graft-versus-host disease (GVHD), and etc. have been established to understand the pathogenic mechanisms of the diseases and to evaluate the efficacy and safety of novel drugs. In this review, I provide an overview of recent advances in the humanized mouse technology, including generation of novel platforms of genetically modified NOG (next generation NOG) mice and some applications of them to create human disease models for drug discovery in preclinical researches.</p>

Journal

Folia Pharmacologica Japonica

Folia Pharmacologica Japonica 151 (4), 160-165, 2018

The Japanese Pharmacological Society

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