The lethal effects of transplantation of Socs1-/- bone marrow cells into irradiated adult syngeneic recipients.
Injection of neonatal bone marrow cells from mice lacking the gene encoding suppressor of cytokine signaling 1 (SOCS1) into irradiated syngeneic 129/Sv or C57BL/6 mice led to a decreased survival, more rapidly occurring in 129/Sv than in C57BL/6 mice. Moribund mice did not exhibit the acute or chronic diseases developed by Socs1-/- mice but developed a pathology characteristic of graft-versus-host disease with typical chronic inflammatory lesions in the liver, skin, lungs, and gut. The results indicate that cells derived from the Socs1-/- bone marrow are autoaggressive but did not identify the cell types involved. Failure of the engrafted Socs1-/- marrow cells to reproduce the tissue damage typical of Socs1-/- disease indicates that loss of SOCS1 from target tissues may also be required for the development of the Socs1-/- diseases, such as fatty degeneration of the liver, polymyositis, or corneal inflammation.
Metcalf
Donald
D
Division of Cancer and Hematology, The Walter and Eliza Hall Institute of Medical Research and the Cooperative Research Centre for Cellular Growth Factors, 1G Royal Parade, Parkville, Victoria 3050, Australia. metcalf@wehi.edu.au
Mifsud
Sandra
S
Di Rago
Ladina
L
Alexander
Warren S
WS
D000818:Animals; D016026:Bone Marrow Transplantation; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology*; D016207:Cytokines / Q000502:physiology; D005804:Genes, Lethal; D006086:Graft vs Host Disease; D007371:Interferon-gamma / Q000502:physiology; D007422:Intestines / Q000473:pathology; D007668:Kidney / Q000473:pathology; D008099:Liver / Q000473:pathology; D008168:Lung / Q000473:pathology; D008221:Lymphoid Tissue / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009206:Myocardium / Q000473:pathology; D011828:Radiation Chimera; D012097:Repressor Proteins; D017634:Self Tolerance; D012867:Skin / Q000473:pathology; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D013950:Thymus Gland / Q000473:pathology; D014185:Transplantation, Isogeneic
D002352:Carrier Proteins; D016207:Cytokines; D012097:Repressor Proteins; C491590:Socs1 protein, mouse; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D007371:Interferon-gamma