ATH-1, A GENE DETERMINING ATHEROSCLEROSIS SUSCEPTIBILITY AND HIGH-DENSITY-LIPOPROTEIN LEVELS IN MICE
ATH-1, A GENE DETERMINING ATHEROSCLEROSIS SUSCEPTIBILITY AND HIGH-DENSITY-LIPOPROTEIN LEVELS IN MICE
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DOI：
10.1073/pnas.84.11.3763
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发表时间：
1987-06-01
影响因子：
11.1
通讯作者：
LEBOEUF, RC
中科院分区：
文献类型：
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作者：
PAIGEN, B;MITCHELL, D;LEBOEUF, RC
高密度脂蛋白 (HDL) 是在喂食含有 4% 脂肪的正常实验室食物的小鼠中发现的主要血浆脂蛋白。当某些近交系的雌性小鼠（例如 C57BL/6）被喂食高脂肪饮食（1.25% 胆固醇、15% 脂肪和 0.5% 胆酸）时，HDL 胆固醇水平下降约 505，并且在 14 周内主动脉形成脂质染色损伤。在其他品系的小鼠中，例如 C3H 和 BALB/c，HDL 脂质水平仅略有下降，并且在 14 周时观察到很少或没有主动脉病变。通过使用源自 C57BL/6 和 BALB/c 以及 C57BL/6 和 C3H/He 的重组近交系分析了这些表型差异的遗传基础。这两种表型作为简单的孟德尔性状分离，并且在它们之间没有观察到重组。因此，HLD-胆固醇水平和对动脉粥样硬化的易感性似乎是由同一基因决定的（或由两个紧密相连的遗传因素决定，两者之间的最大距离为 1.7 厘摩）。该基因被命名为 Ath-1，代表动脉粥样硬化易感性，等位基因 r 代表抵抗，s 代表易感性。 Ath-1 定位在靠近 Alp-2 的 1 号染色体上，Alp-2 是决定载脂蛋白 A-II 结构的基因，载脂蛋白 A-II 是 HDL 中发现的两种主要蛋白质之一。 Ath-1 与 Alp-2 明显可分离，这些基因之间的距离为 6.0 厘摩，标准误差为 4.2 厘摩。在人类中，HDL 水平具有遗传性，并且与动脉粥样硬化呈负相关。家族性高α脂蛋白血症与高密度脂蛋白胆固醇水平和心脏病风险降低有关。人类特征在表型上类似于小鼠的 ATh-1。
High density lipoprotein (HDL) is the major plasma lipoprotein found in mice fed normal laboratory chow containing 4% fat. When female mice from some inbred strains, such as C57BL/6, are fed a high fat diet (1.25% cholesterol, 15% fat, and 0.5% cholic acid), the levels of HDL-cholesterol decrease by about 505, and lipid staining lesions form in the aorta within 14 weeks. In other strains of mice, such as C3H and BALB/c, HDL-lipid levels decrease only slightly, and few or no aortic lesions are observed at 14 weeks. The genetic basis of these phenotypic differences was analyzed by using recombinant inbred strains derived from C57BL/6 and BALB/c and also from C57BL/6 and C3H/He. The two phenotypes segregated as simple Mendelian traits, and no recombination was observed between them. Thus, HLD-cholesterol levels and susceptibility to atherosclerosis appear to be determined by the same gene (or by two closely linked genetic factors that are a maximum of 1.7 centimorgans apart). This gene was named Ath-1, for atherosclerosis susceptibility, with alleles r for resistance and s for susceptibility. Ath-1 maps on chromosome 1 near Alp-2, a gene that determines the structure of apolipoprotein A-II, one of the two major proteins found in HDL. Ath-1 is clearly separable from Alp-2, and the distance between these genes is 6.0 centimorgans with a standard error of 4.2 centimorgans. In humans, levels of HDL are inherited and are inversely correlated with atherosclerosis; familial hyperalphalipoproteinemia is associated with high levels of HDL-cholesterol and decreased risk of heart disease. The human trait phenotypically resembles ATh-1 in the mouse.