Finding of the genes which relate to the atherosclerosis, Using spontaneously hyperlipidemic mice with apolipoprotein E deficiency.

四株自发性高脂血症小鼠：由遗传背景决定的表型差异。自发性高脂血症（SHL）小鼠是载脂蛋白E（Apo E）基因破坏的日本野生小鼠（KOR）。这些小鼠（KOR-Apoe(shl)）是超高胆固醇血症并发展为严重的黄瘤，但与Apo E敲除小鼠相比，它们的动脉粥样硬化相对较轻。首先，我们测试了这种差异是否由于KOR-Apoe中Apoc1和/或Apoc2基因的额外突变（sh1）。南方印迹分析，但没有发现这些基因的严重破坏。接下来，我们测试了表型差异是否是由于遗传背景的差异。为此，我们建立了遗传背景分别为C57BL/6、BALB/c和C3H/He的三种同源SHL小鼠，分别命名为C57BL/6。KOR-Apoe (shl) (B6。KOR-Apoe (shl))、BALB / c。KOR-Apoe(shl) （C.KOR-Apoe(shl)）和C3H/He。KOR-Apoe (shl) (C3.KOR-Apoe (shl))。高胆固醇血症以KOR-Apoe（shl）最为严重，其他依次为：KOR-Apoe (shl) > > C3.KOR-Apoe (shl) > C.KOR-Apoe (shl) > B6.KOR-Apoe (shl)。相反，动脉粥样硬化在B6组最为严重。KOR Apoe（shl）依次为：B6.KOR-Apoe(shl)> . C.KOR-Apoe(shl)>>C3。KOR-Apoe(shl)> or =KOR-Apoe（shl）然而，这个顺序与黄瘤不同，黄瘤在KOR-Apoe（sh1）中非常突出，而在B6中较轻。KOR-Apoe（sh1）、C.KOR-Apoe（sh1）、C3.KORApoe（sh1）。然而，这个顺序与黄瘤不同，黄瘤在KOR-Apoe（sh1）中非常突出，而在B6中较轻。KOR-Apoe（sh1）、C.KOR-Apoe（sh1）、C3.KOR-Apoe（sh1）。这些差异表明，每种表型的严重程度是由不同的遗传背景决定的，这可能是由脂质代谢相关蛋白的多态性组成的。我们发现载脂蛋白A-I在每个SHL菌株中都减少，并且在B6之间多态性。KOR-Apoe（shl）和其他菌株。这种多态性可能与b6中观察到的最严重的动脉粥样硬化（shl）有关。最有可能的是，这些多态性的组合是由于负责表型差异的遗传背景。[J]中华动脉粥样硬化杂志。2001;8(3):71- 79。少

Four strains of spontaneously hyperlipidemic (SHL) mice: phenotypic distinctions determined by genetic backgrounds.Spontaneously hyperlipidemic(SHL) mice are Japanese wild mice (KOR) with disruption of the apolipoprotein E(Apo E) gene. These mice (KOR-Apoe(shl)) are superhypercholesterolemic and develop severe xanthoma, but their atherosclerosis is relatively mild compared with Apo E knockout mice. First, we tested whether this distinction is due to additional mutation of the Apoc1 and/or Apoc2 genes in KOR-Apoe(shl). Southern blot analysis, but found no gross disruption of these genes. Next, we tested whether the phenotypic distinction is due to differences in the genetic background. To this end, we established three lines of congenic SHL mice with a genetic background of C57BL/6,BALB/c or C3H/He, and named them, respectively, C57BL/6.KOR-Apoe(shl) (B6.KOR-Apoe(shl)), BALB/c.KOR-Apoe(shl) (C.KOR-Apoe(shl)) and C3H/He.KOR-Apoe(shl) (C3.KOR-Apoe(shl)). Hypercholesterolemia was most seve … More re in KOR-Apoe(shl) followed the by others as follows; KOR-Apoe(shl)>>C3.KOR-Apoe(shl)>C.KOR-Apoe(shl)>B6.KOR-Apoe(shl). In contrast, atherosclerosis was most severe in B6.KOR Apoe(shl) followed by the others: B6.KOR-Apoe(shl)>C.KOR-Apoe(shl)>>C3.KOR-Apoe(shl)> or =KOR-Apoe(shl). This order, however, did not match that in xanthoma, which was highly prominent in KOR-Apoe(shl) but mild in B6.KOR-Apoe(shl), C.KOR-Apoe(shl) and C3.KORApoe(shl). This order, however, did not match that in xanthoma, which was highly prominant in KOR-Apoe(shl) but mild in B6.KOR-Apoe(shl), C.KOR-Apoe(shl) and C3.KOR-Apoe(shl). These distinctions suggest that the severity of each of the phenotypes is determined by distinct genetic backgrounds which probably are composed of polymorphism of lipid metabolism-related proteins. We found that apolipoprotein A-I is decreased in each SHL strain and polymorphic between B6.KOR-Apoe(shl) and the other strains examined. This polymorphism may be related to the most severe atherosclerosis observed in B6.KOR-Apoe(shl). It is most likely that combination of such polymorphisms is due to the genetic background accountable for phenotype distinctions. J Atheroscler Thromb.2001;8(3):71-9. Less