Polymorphisms of the tumor necrosis factor alpha locus among autoimmune disease susceptible and resistant inbred rat strains.
Inbred rat strains manifest remarkable differences in susceptibility/severity to autoimmune disease. MHC alleles strongly influence the pathogenesis of autoimmune disease in rats, but the precise mechanism(s) remain inadequately defined. The TNFalpha gene is located in the class III region of the MHC. Polymorphisms, influencing either the structure or expression of the TNF protein, might contribute to differences in autoimmune disease susceptibility/severity. We therefore sequenced the Tnf locus using genomic DNA from ACI, BB(DR), BN, DA, F344, and LEW rats that vary in susceptibility/severity to autoimmune diseases. We found 42 polymorphisms among these six strains. Although none of these polymorphisms are predicted to change the amino acid sequence of the TNF protein, several reside in potential non-coding regulatory regions and may influence expression levels. These polymorphisms may serve as good candidates for analysis of TNF expression to elucidate the mechanism(s) by which the MHC regulates susceptibility and/or severity of autoimmune diseases.
Furuya
T
T
Inflammatory Joint Diseases Section, Arthritis and Rheumatism Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH, 9000 Rockville Pike, Building 10, Room 9N240, Bethesda, MD 20892, USA.
Joe
B
B
Salstrom
J L
JL
Hashiramoto
A
A
Dobbins
D E
DE
Wilder
R L
RL
Remmers
E F
EF
D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology*; D001483:Base Sequence; D017931:DNA Primers; D020022:Genetic Predisposition to Disease; D011110:Polymorphism, Genetic; D051381:Rats; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D017931:DNA Primers; D014409:Tumor Necrosis Factor-alpha