Congenic interval of CD45/Ly-5 congenic mice contains multiple genes that may influence hematopoietic stem cell engraftment.
The B6.SJL-Ptprc(d)Pep3(b)/BoyJ (B6.SJL) congenic mouse strain, a valuable and widely used tool in murine bone marrow transplantation studies, has long been considered equivalent to the parental C57B/L6 (B6) strain with the exception of a small congenic interval on chromosome 1 harboring an alternative CD45/Ly-5 alloantigen (Ly-5.1). In this study we compared functional properties of stem and stromal cells between the strains, and delineated the boundary of the B6.SJL congenic interval. We identified a 25% reduction in homing efficiency, 3.8-fold reduction in transplantable long-term hematopoietic stem cells (LT-HSCs), a 5-fold reduction in LT-HSCs capable of 24-hour homing, and a cell-intrinsic engraftment defect of 30% to 50% in B6.SJL-derived bone marrow cells relative to B6-derived cells. These functional differences were independent of stem cell number, cycling, or apoptosis. Genotypic analysis revealed a 42.1-mbp congenic interval in B6.SJL including 306 genes, and at least 124 genetic polymorphisms. Moreover, expression profiling revealed 288 genes differentially expressed between nonhematopoietic stromal cells of the 2 strains. These results indicate that polymorphisms between the B6 and SJL genotype within the B6.SJL congenic interval influence HSC engraftment and result in transcriptional variation within bone marrow stroma.
Waterstrat
Amanda
A
Department of Biological Sciences, Eastern Kentucky University, Richmond, USA.
Liang
Ying
Y
Swiderski
Carol F
CF
Shelton
Brent J
BJ
Van Zant
Gary
G
D000818:Animals; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000276:immunology*; D005838:Genotype; D006085:Graft Survival / Q000235:genetics* / Q000276:immunology*; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000276:immunology*; D017493:Leukocyte Common Antigens / Q000235:genetics / Q000276:immunology*; D051379:Mice; D020297:Mice, Congenic; D011110:Polymorphism, Genetic; D017154:Stromal Cells; D013997:Time Factors; D014184:Transplantation, Homologous
D017493:Leukocyte Common Antigens; C516770:Ptprc protein, mouse