ATHEROSCLEROSIS SUSCEPTIBILITY DIFFERENCES AMONG PROGENITORS OF RECOMBINANT INBRED STRAINS OF MICE
ATHEROSCLEROSIS SUSCEPTIBILITY DIFFERENCES AMONG PROGENITORS OF RECOMBINANT INBRED STRAINS OF MICE
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DOI：
10.1161/01.atv.10.2.316
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发表时间：
1990-03-01
期刊：
影响因子：
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通讯作者：
ALBEE, D
中科院分区：
文献类型：
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作者：
PAIGEN, B;ISHIDA, BY;ALBEE, D
16个近交系小鼠的雌性小鼠被喂以致动脉粥样硬化的食物14周，然后评估主动脉的动脉粥样硬化病变。C57BL/6、C57BR/CD、C57L和SM株对动脉粥样硬化非常敏感，病变面积/主动脉横截面积在4500~8000微米~2之间。菌株C58和SWR的感病能力中等，病斑面积/切片在1670-1690微米~2之间。129株、AKR株、DBA/2株和BALB/c株在20~350µm2/切片范围内仅有微小病变，C3H、NZB、CBA、HRS、SJL和A株14周后无病变。比较了5个菌株在不同时间点的病变形成情况。C57BL/6品系小鼠在7周后出现病变，这些病变继续生长，直到所有小鼠的主动脉和冠状动脉都有大的动脉粥样斑块。AKR和DBA/2菌株早在7或8周就有脂肪条纹皮损，但到14周时这些皮损的大小还没有扩大。BALB/c和C3H菌株在14周时都对病变形成有抵抗力，随着时间的推移，BALB/c和C3H菌株逐渐分化。一年后，BALB/c小鼠出现了较大的病变，而C3H小鼠则没有。大多数选择用于评估的近交系菌株都是重组近交系菌株的祖先，这是一种极大地促进了品系差异分析的遗传工具。这项手术还发现了7组重组近交系菌株，它们的祖细胞在动脉粥样硬化易感性上存在差异：BxD、AKXL、SWXJ、NX8、129XB、NXSM和B6NXAKRN。对这些重组近交系的分析可能会发现更多影响动脉粥样硬化易感性的小鼠基因。
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 .mu.m2. Strains C58 and SWR were intermediate in susceptibility, with lesion area/sections in the range of 1670 to 1690 .mu.m2. Strains 129, AKR, DBA/2, and BALB/c had only small lesions in the range of 20 to 350 .mu.m2/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 surgery 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.