Aw. Roberts et al., Identification of a genetic locus modulating splenomegaly induced by granulocyte colony-stimulating factor in mice, LEUKEMIA, 14(4), 2000, pp. 657-661
Clinically detectable splenomegaly and splenic rupture are uncommon but pot
entially life-threatening consequences of G-CSF administration. Increased s
pleen size in mice injected with G-CSF is a complex genetic trait amenable
to investigation in experimental inter-strain crosses by quantitative trait
analysis. A quantitative trait locus (QTL) with highly significant linkage
(LOD 7.9) for splenomegaly was identified within a 22 centimorgan (cM) reg
ion on chromosome 1. Inheritance of a C57BL/6 haplotype in this region was
associated with a greater spleen weight. The relevance of this locus was co
nfirmed by analysing the responses of mice congenic for the distal 12 cM of
this region (C57BL/6 and C57BL/6.SJL-Ptprc(a) Pep3(b)). Consistent with th
e QTL effect, mice lacking C57BL/6 alleles in this region had reduced splen
omegaly induced by G-CSF. Intriguingly, peripheral brood neutrophilia and p
rogenitor cell mobilisation responses to G-CSF were also significantly infl
uenced.