Endotoxin induced uveitis in the mouse: susceptibility and genetic control.
Endotoxin induced uveitis in the mouse provides a useful animal model for acute anterior uveitis in humans. We have investigated the susceptibility of endotoxin-induced uveitis among various mouse strains, and have examined the relationship between genetic background and the resultant inflammatory response to endotoxin. We studied ten strains with differing major histocompatibility-2 genes, lipopolysaccharide response gene, and strains with mast cell depletion and its sham control. Anterior uveitis was induced by injecting 300 micrograms of Salmonella typhimurium endotoxin into one hind footpad. Mice were then killed 8, 12, 16, 20, 24, 48 and 72 hr after endotoxin injection, and vertical sections of the eyes through the pupil-optic nerve axis were evaluated for ocular inflammation. C3H/HeN mice developed severe uveitis. In contrast, C3H/HeJ mice (lipopolysaccharide response gene-) did not develop uveitis even though it has the same genetic background and shares the same major histocompatibility-2 haplotype with C3H/HeN mice (lipopolysaccharide response gene+). The strain that was mast-cell deficient (W/Wv) developed minimal uveitis; however, W/+ mice, with mast cells, developed more inflammation at 48 and 72 hr after endotoxin injection. C3H.SW and FVB/N mice also developed severe uveitis, and BALB/C, CBA/J, and B10.A developed mild uveitis. In conclusion, there is a wide variation in the magnitude and susceptibility to endotoxin among mouse strains. Multiple factors appear to influence this variability, including non-histocompatibility-2 genetic background, the lipopolysaccharide response gene, and the presence of mast cells.
Li
Q
Q
Laboratory of Immunology and Clinical Branch, NEI, NIH, Bethesda, MD 20892-1858, USA.
Peng
B
B
Whitcup
S M
SM
Jang
S U
SU
Chan
C C
CC
D000818:Animals; D001427:Bacterial Toxins; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D004731:Endotoxins; D005260:Female; D006239:Haplotypes; D008070:Lipopolysaccharides; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008808:Mice, Inbred CBA; D013045:Species Specificity; D014605:Uveitis / Q000209:etiology / Q000235:genetics*
D001427:Bacterial Toxins; D004731:Endotoxins; D008070:Lipopolysaccharides; C027952:salmonella toxin