QTL analyses of lineage-negative mouse bone marrow cells labeled with Sca-1 and c-Kit

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 F2 mice to analyse lineage negative (Lin-) bone marrow cells according to the intensity of labelling with Sca-1 and c-Kit. In the Lin- Sca-1+ c-Kit+ enriched population six quantitative trait loci (QTL) were identified – one significant and five suggestive. Whereas previous in vitro clonogenic, LTIC-IC, CAFC day 35, and flow cytometry each identified different QTL, our approach identified the same or very similar QTL at all three loci (Chromosome 1, 17 and 18) as well as QTL on chromosomes 6 and 10. In silico analyses implicate haematopoietic stem cell homing involving Cxcr4 and Cxcl12 as being the determining pathway. The mapping of the same or very similar QTLs 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 sub-populations can be functionally, phenotypically and genetically defined.