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

J Immunol Methods. 2018 Jun:457:66-72. doi: 10.1016/j.jim.2018.03.016. Epub 2018 Apr 6.

Abstract

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.

Keywords: Bone marrow; C-myb; Chimera; Conditional deletion; Hematopoietic stem cells; Transplantation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Marrow Transplantation / methods*
  • Female
  • Gene Deletion*
  • Genes, myb / genetics*
  • Hematopoietic Stem Cell Transplantation / methods*
  • Immune Tolerance
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Poly I-C / administration & dosage
  • Radiation, Ionizing
  • Transplantation Chimera*
  • Transplantation Conditioning
  • Transplantation, Homologous

Substances

  • Poly I-C