Atherosclerosis susceptibility differences among progenitors of recombinant inbred strains of mice.

Abstract

Female mice of 16 inbred mouse strains were fed an atherogenic diet for 14 weeks and were then evaluated for atherosclerotic lesions in the aorta. Strains C57BL/6, C57BR/cd, C57L, and SM were very susceptible to atherosclerosis, with lesion area/aortic cross-sections in the range of 4500 to 8000 microns 2. Strains C58 and SWR were intermediate in susceptibility, with lesion area/sections in the range of 1670 to 1690 microns 2. Strains 129, AKR, DBA/2, and BALB/c had only small lesions in the range of 20 to 350 microns 2/section; strains C3H, NZB, CBA, HRS, SJL, and A had no lesions after 14 weeks. Lesion formation in five strains was compared at several time points. Strain C57BL/6 mice developed lesions by 7 weeks, and these continued to grow until all mice had large atheromatous plaques in the aorta and coronary arteries. Strains AKR and DBA/2 also had fatty streak lesions as early as 7 or 8 weeks, but these lesions had not progressed in size by 14 weeks. Strains BALB/c and C3H, which were both resistant to lesion formation at 14 weeks, diverged from each other as time progressed. By 1 year, BALB/c mice had large lesions, but C3H mice had none. Most of the inbred strains chosen for evaluation are the progenitors of recombinant inbred sets of strains, a genetic tool that greatly facilitates the analysis of strain differences. This survey indicates seven additional recombinant inbred sets of strains whose progenitors differ in atherosclerosis susceptibility: BXD, AKXL, SWXJ, NX8, 129XB, NXSM, and B6NXAKRN. An analysis of these recombinant inbred strains may reveal additional mouse genes affecting atherosclerosis susceptibility.