Polymorphic Sirpa is the genetic determinant for NOD-based mouse lines to achieve efficient human cell engraftment

Takuji Yamauchi, Katsuto Takenaka, Shingo Urata, Takahiro Shima, Yoshikane Kikushige, Takahito Tokuyama, Chika Iwamoto, Mariko Nishihara, Hiromi Iwasaki, Toshihiro Miyamoto, Nakayuki Honma, Miki Nakao, Takashi Matozaki, Koichi Akashi

Research output: Contribution to journalArticle

63 Citations (Scopus)

Abstract

Current mouse lines efficient for human cell xenotransplantation are backcrossed into NOD mice to introduce its multiple immunodeficient phenotypes. Our positional genetic study has located the NOD-specific polymorphic Sirpa as a molecule responsible for its high xenograft efficiency: it recognizes human CD47 and the resultant signaling may cause NOD macrophages not to engulf human grafts. In the present study, we established C57BL/6.Rag2 null//2rgnull mice harboring NOD-Sirpa (BRGS). BRGS mice engrafted human hematopoiesis with an efficiency that was equal to or even better than that of the NOD.Rag1null//2rgnull strain, one of the best xenograft models. Consequently, BRGS mice are free from other NOD-related abnormalities; for example, they have normalized C5 function that enables the evaluation of complement-dependent cytotoxicity of antibodies against human grafts in the humanized mouse model. Our data show that efficient human cell engraftment found in NOD-based models is mounted solely by their polymorphic Sirpa. The simplified BRGS line should be very useful in future studies of human stem cell biology.

Original languageEnglish
Pages (from-to)1316-1325
Number of pages10
JournalBlood
Volume121
Issue number8
DOIs
Publication statusPublished - Feb 21 2013

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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