Genetic analysis of progenitor cell mobilization by granulocyte colony-stimulating factor: verification and mechanisms for loci on murine chromosomes 2 and 11.
OBJECTIVE
It is notable that there is significant inter-individual variability in humans and inter-strain variability in mice in the ability to mobilize hematopoietic stem and progenitor cells, suggesting that there is genetic regulation of mobilization. In the murine system, loci on chromosomes 2 and 11 have been linked to an inter-strain variation in granulocyte colonystimulating factor (G-CSF)-induced stem cell mobilization proficiency. The aim of this study was to verify this linkage and to gain insight into the function of these loci.


METHODS
Animals congenic for the loci on chromosomes 2 and 11 were generated by a speed-congenic approach and the function of the loci were further analyzed in doubly congenic animals and with a competitive transplantation/mobilization protocol.


RESULTS
The analysis of congenic animals verified that both loci are linked to mobilization proficiency. Analysis of mobilization in doubly congenic animals suggested that both loci act in the same regulatory pathway. Mobilization experiments conducted with mice that had previously been competitively repopulated with congenic and parental-strain BM revealed that the locus on chromosome 11 operates via a progenitor cell-intrinsic mechanism.


CONCLUSIONS
We confirmed linkage of loci on chromosomes 2 and 11 to G-CSF-induced mobilization and thus validated their role as regulators of hematopoietic progenitor cell mobilization in mice. These findings will be useful for further studies directed at identifying genes that regulate mobilization proficiency.
Geiger
Hartmut
H
Department of Internal Medicine, University of Kentucky Medical Center, Lexington, Ky., USA. Hartmut.Geiger@chmcc.org
Szilvassy
Stephen J
SJ
Ragland
Penny
P
Van Zant
Gary
G
D000818:Animals; D002874:Chromosome Mapping; D008040:Genetic Linkage; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D019650:Hematopoietic Stem Cell Mobilization; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA
D016179:Granulocyte Colony-Stimulating Factor