Inducible disruption of the c-myb gene allows allogeneic bone marrow transplantation without irradiation

被引:5
作者
Stremmel, C. [1 ,2 ]
Schuchert, R. [1 ,2 ]
Schneider, V [1 ,2 ]
Weinberger, T. [1 ,2 ]
Thaler, R. [1 ,2 ]
Messerer, D. [1 ,2 ]
Helmer, S. [1 ,2 ]
Geissmann, F. [3 ]
Frampton, J. [4 ]
Massberg, S. [1 ,2 ,5 ]
Schulz, C. [1 ,2 ,5 ]
机构
[1] Ludwig Maximilians Univ Munchen, Klinikum Univ, Med Klin & Poliklin 1, Marchioninistr 15, D-81377 Munich, Germany
[2] Ludwig Maximilians Univ Munchen, Walter Brendel Ctr Expt Med, Marchioninistr 15, D-81377 Munich, Germany
[3] Mem Sloan Kettering Canc Ctr, Immunol Program, New York, NY 10065 USA
[4] Univ Birmingham, Coll Med & Dent Sci, Inst Canc & Genom Sci, Birmingham B15 2TT, W Midlands, England
[5] DZHK German Ctr Cardiovasc Res, Partner Site Munich, Heart Alliance, Biedersteiner Str 29, D-80802 Munich, Germany
关键词
Bone marrow; Transplantation; Hematopoietic stem cells; Chimera; C-myb; Conditional deletion; HEMATOPOIETIC STEM-CELLS; EPIDERMAL LANGERHANS CELLS; INDUCED LIVER-INJURY; TOLL-LIKE RECEPTOR-3; DOUBLE-STRANDED-RNA; SELF-RENEWAL; BODY IRRADIATION; RECIPIENT MICE; ADULT LIFE; IN-VIVO;
D O I
10.1016/j.jim.2018.03.016
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
Allogeneic bone marrow (BM) transplantation enables the in vivo functional assessment of hematopoietic cells. As pre-conditioning, ionizing radiation is commonly applied to induce BM depletion, however, it exerts adverse effects on the animal and can limit experimental outcome. Here, we provide an alternative method that harnesses conditional gene deletion to ablate c-myb and thereby deplete BM cells, hence allowing BM substitution without other pre-conditioning. The protocol results in a high level of blood chimerism after allogeneic BM transplantation, whereas immune cells in peripheral tissues such as resident macrophages are not replaced. Further, mice featuring a low chimerism after initial transplantation can undergo a second induction cycle for efficient deletion of residual BM cells without the necessity to re-apply donor cells. In summary, we present an effective c-myb-dependent genetic technique to generate BM chimeras in the absence of irradiation or other methods for pre-conditioning.
引用
收藏
页码:66 / 72
页数:7
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