Identification of a genetic locus modulating splenomegaly induced by granulocyte colony-stimulating factor in mice.
Clinically detectable splenomegaly and splenic rupture are uncommon but potentially life-threatening consequences of G-CSF administration. Increased spleen 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) region 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 confirmed 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 the QTL effect, mice lacking C57BL/6 alleles in this region had reduced splenomegaly induced by G-CSF. Intriguingly, peripheral blood neutrophilia and progenitor cell mobilisation responses to G-CSF were also significantly influenced.
Roberts
A W
AW
Division of Haematology and Cancer Research, The Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Victoria, Australia.
Hasegawa
M
M
Metcalf
D
D
Foote
S J
SJ
D000818:Animals; D002874:Chromosome Mapping; D003433:Crosses, Genetic; D005260:Female; D020022:Genetic Predisposition to Disease; D016179:Granulocyte Colony-Stimulating Factor / Q000633:toxicity*; D019650:Hematopoietic Stem Cell Mobilization; D006801:Humans; D000078224:Lenograstim; D008126:Lod Score; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D009929:Organ Size; D019655:Quantitative Trait, Heritable; D011994:Recombinant Proteins / Q000633:toxicity; D013047:Specific Pathogen-Free Organisms; D013154:Spleen / Q000473:pathology; D013163:Splenomegaly / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology
D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D000078224:Lenograstim