Pbrgcsf1^DBA/2J
QTL Variant Detail

Summary

• QTL variant: Pbrgcsf1^DBA/2J
• Name: peripheral blood stem cell response to granulocyte colony stimulating factor 1; DBA/2J
• MGI ID: MGI:2447053
• QTL: Pbrgcsf1 Location: Chr2:123233580-123233729 bp Genetic Position: Chr2, cM position of peak correlated region/allele: 60.69 cM
• QTL Note: genome coordinates based on the marker associated with the peak LOD score

Variant origin

• Strain of Specimen: DBA/2J

Variant description

• Allele Type: QTL
• Mutation: Undefined
• Mutation details: This allele confers increased G-CSF induced peripheral blood stem cell mobilization compared to C57BL/6J. (J:87464)

Notes

Mapping and Phenotype information for this QTL, its variants and associated markers

J:79266

Peripheral blood stem cell response to granulocyte colony stimulating factor (G-CSF) differed between C57BL/6J and DBA/2J. In the DBA/2J strain G-CSF mobilized the progenitor cells into the peripheral blood more effectively then did C57BL/6J. The difference in strains enabled the mapping of the quantitative phenotype in the mouse genome. One locus Pbrgcsf1 was identified as mapping with D2Mit255 on mouse Chromosome 2 by using 260 backcross mice derived using strains C57BL/6J and DBA/2J. A possible candidate in the Chromosome 2 QTL region was identified as Hdc, histidine decarboxylase at approximately 71 cM. In addition the BXD RI strains proved useful in identifying a second QTL Pbrgcsf2 on mouse Chromosome 11. Pbrgcsf2 locus was associated with D11Ncvs42. A possible candidate in the Chromosome 11 QTL region was identified as Tcn2, transcobalamin 2 at 3 cMs.

J:87464

Two previously identified QTLs associated with G-CSF induced stem cell mobilization, Pbrgcsf1 and Pbrgcsf2, were confirmed in this study. Pbrgcsf1 maps to 69 cM on mouse Chromosome 2 and Pbrgcsf2 maps to 4 cM on mouse Chromosome 11. Single and double congenic strains were constructed by introgressing DBA/2J-derived donor DNA at Pbrgcsf1 and/or Pbrgcsf2 onto a C57BL/6J genetic background for 6 to 7 generations. The Pbrgcsf1 congenic interval spans 70 cM - 105 cM and is derived from donor recombinant inbred strain BXD-31. The Pbrgcsf2 congenic interval spans 0 cM - 18 cM and is derived from donor recombinant inbred strain BXD-24. Progenitor strain DBA/2J is a "high responder" to G-CSF induced stem cell mobilization whereas progenitor strain C57BL/6J is a "low responder".

Animals congenic for the Pbrgcsf2 locus at mouse Chromosome 11 exhibit increased stem cell mobilization following G-CSF stimulation whereas animals congenic for the Pbrgcsf1 locus on mouse Chromosome 2 does not. Animals heterozygous for Pbrgcsf1 and/or Pbrgcsf2 exhibit increased stem cell mobilization following G-CSF stimulation. Authors state that these phenotypes are consistent with the original identification of Pbrgcsf1 and Pbrgcsf2.

References

• Original: J:79266 Hasegawa M, et al., Progenitor cell mobilization by granulocyte colony-stimulating factor controlled by loci on chromosomes 2 and 11. Blood. 2000 Mar 1;95(5):1872-4
• All: 2 reference(s)