Genetic background selectively influences innominate artery atherosclerosis: immune system deficiency as a probe.
OBJECTIVE
We sought to examine whether there is a site-specific effect on atherosclerosis of the absence of mature T and B cells caused by a recombination activating-gene deficiency in LDL receptor-deficient mice and whether this effect is influence by the extent of backcrossing to C57BL/6 mice.


RESULTS
Male mice were fed atherogenic diets for 3 months. In strain 1 mice, in which approximately 93% of the genes were from C57BL/6 mice, the absence of mature T and B cells led to a significant reduction in atherosclerosis in both the aortic sinus and the innominate artery. In strain 2 mice, in which approximately 99+% of the genes were from C57BL/6 mice, immune system deficiency led to a site-specific effect on atherosclerosis, with a reduction in atherosclerosis in the aortic sinus but not in the innominate artery, similar to previous results obtained with apolipoprotein E-/- mice. All of the immune system-incompetent mice had lower plasma total and VLDL cholesterol levels regardless of strain or diet, indicating that differences in lipid levels were unlikely to be responsible for these site-specific effects of immune system deficiency.


CONCLUSIONS
These results suggest that immune system deficiency has a site-specific effect on atherosclerosis that is sensitive to the genetic background of the mice.
Reardon
Catherine A
CA
Department of Pathology, University of Chicago, 5841 S Maryland Ave, Chicago, IL 60637, USA. reardon@midway.uchicago.edu
Blachowicz
Lydia
L
Lukens
John
J
Nissenbaum
Michael
M
Getz
Godfrey S
GS
D000818:Animals; D001161:Arteriosclerosis / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology; D016122:Brachiocephalic Trunk; D015243:Cholesterol, VLDL / Q000097:blood; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000378:metabolism; D007153:Immunologic Deficiency Syndromes / Q000503:physiopathology; D008055:Lipids / Q000097:blood; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011973:Receptors, LDL / Q000172:deficiency / Q000235:genetics*; D013601:T-Lymphocytes / Q000276:immunology
D015243:Cholesterol, VLDL; D004268:DNA-Binding Proteins; D008055:Lipids; C499308:Rag2 protein, mouse; D011973:Receptors, LDL; C064655:V(D)J recombination activating protein 2