Genetic control of in vivo tumor necrosis factor production in mice.
We report on the genetic effect on in vivo production of tumor necrosis factor (TNF)-alpha induced by lipopolysaccharides (LPS) using various congenic mouse strains. B10.A, Bl0.A(3R), B10.AQR, B10.A(5R), and B10.S(7R) produced significantly high TNF-alpha compared with B10.BR, B10.S, C57BL/10, B10.A(2R), B10.A(4R), B10.G, B10.DA(80NS), and B10.RIII(71NS). This suggests that LPS-induced TNF-alpha production is genetically controlled by H-2. Mice with the same alleles on K, A, E, or S loci produced various (high or low) levels of TNF-alpha, thus indicating that regulatory genes are located outside these loci. All strains with H-2Dd produced significantly high levels of TNF-alpha, but strains with other alleles in the H-2D locus produced low levels. Thus, TNF-alpha production appears to be genetically linked to H-2D itself or H-2D linked genes and the allele d is linked to a high responder gene. This was the case with the A background. C3H/HeN (H-2k), however, showed a high TNF-alpha production, suggesting the presence of another controlling gene outside H-2. In addition, high TNF-alpha productivity was transmitted into F1 mice (B10.A X B10.BR) in a dominant fashion. Both LPS-stimulated and unstimulated TNF-alpha mRNA expression in splenic macrophages were enhanced in high responder strains. Thus, we conclude that TNF-alpha production is closely related to genes within or linked to the H-2D locus as well as others outside H-2.
Yamakawa
T
T
Third Department of Internal Medicine, Yokohama City University School of Medicine, Japan.
Tanaka
S I
SI
Yamakawa
Y
Y
Isoda
F
F
Kawamoto
S
S
Fukushima
J
J
Minami
M
M
Okuda
K
K
Sekihara
H
H
D000818:Animals; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D005799:Genes, Dominant; D005809:Genes, Regulator; D006183:H-2 Antigens; D006239:Haplotypes; D006579:Heterozygote; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D012333:RNA, Messenger / Q000235:genetics; D013154:Spleen / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D006183:H-2 Antigens; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha