Effects of excess GM-CSF levels on hematopoiesis and leukemia development in GM-CSF/max 41 double transgenic mice.
Double transgenic mice were produced by mating granulocyte-macrophage colony-stimulation factor (GM-CSF) transgenic mice with max 41 transgenic mice that exhibit excess granulopoiesis and a predisposition to thymic lymphoma development. Although only two-thirds of the double transgenic mice had elevated circulating GM-CSF levels, double transgenic mice maintained significantly higher blood granulocytes and monocytes and more extreme granulopoietic hypercellularity in the marrow and spleen than max 41 transgenic mice. In double transgenic mice, early death occurred from the GM-CSF transgenic syndrome. Because of these early deaths, the incidence of thymic and generalized lymphomas was artificially lower than in max 41 mice but those lymphomas that did develop occurred earlier than in max 41 mice. While the excess GM-CSF levels in double transgenic mice stimulated increased granulocyte and monocyte formation and peritoneal dendritic cells were excessive, this failed to prevent the spontaneous development of T lymphomas, suggesting that dendritic cell-initiated suppression of tumor development may not be effective with this type of tumor.
Metcalf
D
D
Walter and Eliza Hall Institute of Medical Research, PO Royal Melbourne Hospital, Victoria, Australia.
Shortman
K
K
Vremec
D
D
Mifsud
S
S
Di Rago
L
L
D000818:Animals; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D050976:Basic-Leucine Zipper Transcription Factors; D001853:Bone Marrow / Q000276:immunology; D001854:Bone Marrow Cells; D002478:Cells, Cultured; D003433:Crosses, Genetic; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis* / Q000235:genetics; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism*; D007942:Leukemia, Experimental / Q000235:genetics* / Q000276:immunology / Q000503:physiopathology; D008198:Lymph Nodes / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D013154:Spleen / Q000166:cytology / Q000276:immunology; D014157:Transcription Factors / Q000096:biosynthesis
D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D050976:Basic-Leucine Zipper Transcription Factors; D004268:DNA-Binding Proteins; C067850:Myc associated factor X; D014157:Transcription Factors; C068422:Max protein, mouse; D016178:Granulocyte-Macrophage Colony-Stimulating Factor