| First Author | Jinnouchi F | Year | 2020 |
| Journal | Blood | Volume | 135 |
| Issue | 19 | Pages | 1661-1672 |
| PubMed ID | 32206775 | Mgi Jnum | J:289543 |
| Mgi Id | MGI:6432731 | Doi | 10.1182/blood.2019002194 |
| Citation | Jinnouchi F, et al. (2020) A human SIRPA knock-in xenograft mouse model to study human hematopoietic and cancer stem cells. Blood 135(19):1661-1672 |
| abstractText | In human-to-mouse xenogeneic transplantation, polymorphisms of signal-regulatory protein alpha (SIRPA) that decide their binding affinity for human CD47 are critical for engraftment efficiency of human cells. In this study, we generated a new C57BL/6.Rag2nullIl2rgnull (BRG) mouse line with Sirpahuman/human (BRGShuman) mice, in which mouse Sirpa was replaced by human SIRPA encompassing all 8 exons. Macrophages from C57BL/6 mice harboring Sirpahuman/human had a significantly stronger affinity for human CD47 than those harboring SirpaNOD/NOD and did not show detectable phagocytosis against human hematopoietic stem cells. In turn, Sirpahuman/human macrophages had a moderate affinity for mouse CD47, and BRGShuman mice did not exhibit the blood cytopenia that was seen in Sirpa-/- mice. In human to mouse xenograft experiments, BRGShuman mice showed significantly greater engraftment and maintenance of human hematopoiesis with a high level of myeloid reconstitution, as well as improved reconstitution in peripheral tissues, compared with BRG mice harboring SirpaNOD/NOD (BRGSNOD). BRGShuman mice also showed significantly enhanced engraftment and growth of acute myeloid leukemia and subcutaneously transplanted human colon cancer cells compared with BRGSNOD mice. BRGShuman mice should be a useful basic line for establishing a more authentic xenotransplantation model to study normal and malignant human stem cells. |
