| First Author | Johansson MH | Year | 2006 |
| Journal | J Immunol | Volume | 177 |
| Issue | 11 | Pages | 7923-9 |
| PubMed ID | 17114464 | Mgi Jnum | J:116666 |
| Mgi Id | MGI:3694793 | Doi | 10.4049/jimmunol.177.11.7923 |
| Citation | Johansson MH, et al. (2006) Mapping of quantitative trait loci determining NK cell-mediated resistance to MHC class I-deficient bone marrow grafts in perforin-deficient mice. J Immunol 177(11):7923-9 |
| abstractText | NK cells reject allogeneic and MHC class I-deficient bone marrow (BM) grafts in vivo. The mechanisms used by NK cells to mediate this rejection are not yet thoroughly characterized. Although perforin plays a major role, perforin-independent mechanisms are involved as well. C57BL/6 mice deficient in perforin (B6 perforin knockout (PKO)) reject class I-deficient TAP-1 KO BM cells as efficiently as normal B6 mice. In contrast, perforin-deficient 129S6/SvEvTac mice (129 PKO) cannot mediate this rejection while normal 129 mice efficiently reject. This suggests that in 129, but not in B6, mice, perforin is crucial for NK cell-mediated rejection of MHC class I-deficient BM grafts. To identify loci linked to BM rejection in perforin-deficient mice, we generated backcross 1 progeny by crossing (129 x B6)F(1) PKO mice to 129 PKO mice. In transplantation experiments, >350 backcross 1 progeny were analyzed and displayed a great variation in ability to reject TAP-1 KO BM grafts. PCR-based microsatellite mapping identified four quantitative trait loci (QTL) on chromosomes 2, 4, and 8, with the QTL on chromosome 8 showing the highest significance, as well as a fifth epistatic QTL on chromosome 3. This study describes the first important step toward identifying BM graft resistance gene(s). |
