title: QTL analyses of lineage-negative mouse bone marrow cells labeled with Sca-1 and c-Kit.
abstract: Differences in the number of functionally and/or phenotypically defined bone marrow cells in inbred mouse strains have been exploited to map quantitative trait loci (QTL) that determine the variation in cell frequency. To extend this approach to the differences in the stem/progenitor cell compartment in CBA/H and C57BL/6 mice, we have exploited the resolution of flow cytometry and the power of QTL analyses in 124 F(2) mice to analyze lineage-negative (Lin(-)) bone marrow cells according to the intensity of labeling with Sca-1 and c-Kit. In the Lin(-) Sca-1(+) c-Kit(+) enriched population, six QTL were identified: one significant and five suggestive. Whereas previous in vitro clonogenic, LTC-IC, day 35 CAFC, and flow cytometry each identified different QTL, our approach identified the same or very similar QTL at all three loci (chromosomes 1, 17, and 18) as well as QTL on chromosomes 6 and 10. In silico analyses implicate hematopoietic stem cell homing involving Cxcr4 and Cxcl12 as being the determining pathway. The mapping of the same or very similar QTL in independent studies using different assay(s) suggests a common genetic determinant, and thus reinforces the biological and genetic significance of the QTL. These data also suggest that mouse bone marrow cell subpopulations can be functionally, phenotypically, and genetically defined.
authors.affiliation: Department of Genetics, University of Leicester, University Road, Leicester LE1 7RH, UK.
authors.forename: Mays
authors.initials: M
authors.lastname: Jawad
authors.forename: Clare
authors.initials: C
authors.lastname: Cole
authors.forename: Abigail
authors.initials: A
authors.lastname: Zanker
authors.forename: George
authors.initials: G
authors.lastname: Giotopoulos
authors.forename: Simon
authors.initials: S
authors.lastname: Fitch
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Talbot
authors.forename: Mark
authors.initials: M
authors.lastname: Plumb
mesh_terms: D000818:Animals; D000950:Antigens, Ly / Q000378:metabolism*; D001854:Bone Marrow Cells / Q000166:cytology* / Q000378:metabolism; D002454:Cell Differentiation; D019070:Cell Lineage; D054377:Chemokine CXCL12 / Q000378:metabolism; D005434:Flow Cytometry; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism*; D040641:Quantitative Trait Loci; D019718:Receptors, CXCR4 / Q000378:metabolism; D013045:Species Specificity
chemical_list: D000950:Antigens, Ly; C514936:CXCR4 protein, mouse; D054377:Chemokine CXCL12; C515256:Cxcl12 protein, mouse; C074650:Ly6a protein, mouse; D008565:Membrane Proteins; D019718:Receptors, CXCR4; D019009:Proto-Oncogene Proteins c-kit