Decreased expression of Fli-1 in bone marrow-derived haematopoietic cells significantly affects disease development in Murphy Roths Large/lymphoproliferation (MRL/lpr) mice.
The transcription factor Fli-1 is implicated in the pathogenesis of both murine and human lupus. Decreased expression of Fli-1 in heterozygous (Fli-1(+/-)) Murphy Roths Large (MRL)/lpr mice resulted in significantly lower kidney pathological scores and markedly increased survival. In this study, bone marrow (BM) transplantation was used to investigate the role of decreased expression of Fli-1 in haematopoietic versus non-haematopoietic cell lineages in autoimmune disease development. Wild-type (WT) MRL/lpr that received BM from Fli-1(+/-) MRL/lpr mice had statistically significantly lower autoantibodies, less proteinuria, reduced renal disease and prolonged survival compared to WT MRL/lpr mice that received BM from WT MRL/lpr mice. Although not statistically significant, Fli-1(+/-) MRL/lpr mice that received BM from WT MRL/lpr mice also had lower autoantibodies and improved survival compared to WT MRL/lpr mice that received BM from WT MRL/lpr mice. Our data indicate that expression of Fli-1 in haematopoietic cell lineages has a significant effect on disease development in MRL/lpr mice.
Molano
I
I
Department of Medicine, Division of Rheumatology & Immunology, Medical University of South Carolina, Charleston, SC 29425-6370, USA.
Mathenia
J
J
Ruiz
P
P
Gilkeson
G S
GS
Zhang
X K
XK
D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis / Q000097:blood; D016026:Bone Marrow Transplantation; D019070:Cell Lineage; D018450:Disease Progression; D005260:Female; D006412:Hematopoietic Stem Cells / Q000378:metabolism; D006579:Heterozygote; D007668:Kidney / Q000473:pathology; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D008181:Lupus Nephritis / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000628:therapy; D008297:Male; D051379:Mice; D019463:Mice, Inbred MRL lpr; D051789:Proto-Oncogene Protein c-fli-1 / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D011828:Radiation Chimera; D013047:Specific Pathogen-Free Organisms
D001323:Autoantibodies; C497426:Fli1 protein, mouse; D051789:Proto-Oncogene Protein c-fli-1