A chromosome 16 quantitative trait locus regulates allogeneic bone marrow engraftment in nonmyeloablated mice.
Identifying genes that regulate bone marrow (BM) engraftment may reveal molecular targets for overcoming engraftment barriers. To achieve this aim, we applied a forward genetic approach in a mouse model of nonmyeloablative BM transplantation. We evaluated engraftment of allogeneic and syngeneic BM in BALB.K and B10.BR recipients. This allowed us to partition engraftment resistance into its intermediate phenotypes, which are firstly the immune-mediated resistance and secondly the nonimmune rejection of donor BM cells. We observed that BALB.K and B10.BR mice differed with regard to each of these resistance mechanisms, thereby providing evidence that both are under genetic control. We then generated a segregating backcross (n = 200) between the BALB.K and B10.BR strains to analyze for genetic linkage to the allogeneic BM engraftment phenotype using a 127-marker genome scan. This analysis identified a novel quantitative trait locus (QTL) on chromosome 16, termed Bmgr5 (logarithm of odds 6.4, at 11.1 cM). The QTL encodes susceptibility alleles, from the BALB.K strain, that are permissive for allogeneic BM engraftment. Further identification of Bmgr5 genes by positional cloning may reveal new and effective approaches for overcoming BM engraftment obstacles.
Cao
Thai M
TM
Department of Medicine, University of Utah, Salt Lake City, UT 84132, USA. thai.cao@hsc.utah.edu
Thomas
Alun
A
Wang
Yuanyuan
Y
Tsai
Schickwann
S
Logronio
Kathryn
K
Shizuru
Judith A
JA
D000818:Animals; D000831:Animals, Newborn; D016026:Bone Marrow Transplantation; D002874:Chromosome Mapping; D005260:Female; D006084:Graft Rejection / Q000235:genetics; D006085:Graft Survival / Q000235:genetics*; D016027:Heart Transplantation; D018380:Hematopoietic Stem Cell Transplantation; D007178:Inbreeding; D008297:Male; D051379:Mice; D008806:Mice, Inbred AKR; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D040641:Quantitative Trait Loci; D018183:Transplantation Chimera / Q000235:genetics; D014184:Transplantation, Homologous