Mutational analysis of TNF-alpha gene reveals a regulatory role for the 3'-untranslated region in the genetic predisposition to lupus-like autoimmune disease.
Lupus-prone mice show reduced production of TNF-alpha and, upon long-term treatment with recombinant TNF-alpha, significant protection from disease development. Mutational analysis of the 5'-untranslated region (UTR) and 3'-UTR of the mouse TNF-alpha gene reveals a marked degree of polymorphism. Transient expression experiments in the RAW 264.7 macrophage-like cell line using the luciferase reporter system suggest an important role for the mutations in the 3'-UTR in the biosynthesis of TNF-alpha, and provide a molecular explanation for the reduced TNF-alpha production in lupus-prone NZW mice.
Jacob
C O
CO
Department of Medicine, University of Southern California School of Medicine, Los Angeles, CA 90033, USA.
Lee
S K
SK
Strassmann
G
G
D000818:Animals; D001483:Base Sequence; D004252:DNA Mutational Analysis; D004198:Disease Susceptibility; D005786:Gene Expression Regulation / Q000276:immunology*; D008180:Lupus Erythematosus, Systemic / Q000235:genetics* / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D008814:Mice, Inbred NZB; D008969:Molecular Sequence Data; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics* / Q000276:immunology
D014409:Tumor Necrosis Factor-alpha