Abstract:
:Mice repopulated with human hematopoietic cells are a powerful tool for the study of human hematopoiesis and immune function in vivo. However, existing humanized mouse models cannot support development of human innate immune cells, including myeloid cells and natural killer (NK) cells. Here we describe two mouse strains called MITRG and MISTRG, in which human versions of four genes encoding cytokines important for innate immune cell development are knocked into their respective mouse loci. The human cytokines support the development and function of monocytes, macrophages and NK cells derived from human fetal liver or adult CD34(+) progenitor cells injected into the mice. Human macrophages infiltrated a human tumor xenograft in MITRG and MISTRG mice in a manner resembling that observed in tumors obtained from human patients. This humanized mouse model may be used to model the human immune system in scenarios of health and pathology, and may enable evaluation of therapeutic candidates in an in vivo setting relevant to human physiology.
journal_name
Nat Biotechnoljournal_title
Nature biotechnologyauthors
Rongvaux A,Willinger T,Martinek J,Strowig T,Gearty SV,Teichmann LL,Saito Y,Marches F,Halene S,Palucka AK,Manz MG,Flavell RAdoi
10.1038/nbt.2858subject
Has Abstractpub_date
2014-04-01 00:00:00pages
364-72issue
4eissn
1087-0156issn
1546-1696pii
nbt.2858journal_volume
32pub_type
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