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

四个品系的自发性高脂血症(SHL)小鼠：由遗传背景决定的表型差异。自发性高脂血症(SHL)小鼠是具有载脂蛋白E(Apo E)基因缺失的日本野鼠(KOR)。这些小鼠(KOR-APOE(Shl))是高胆固醇血症，并发展为严重的黄色瘤，但与Apo E基因敲除的小鼠相比，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是由于KOR-APOE(Shl)中apoc1和/或apoc2基因的额外突变所致。Southern杂交分析，但没有发现这些基因的严重干扰。接下来，我们测试了表型差异是否源于遗传背景的差异。为此，我们建立了3个遗传背景为C57BL/6、BALB/c和C3H/He的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))。高胆固醇血症是最严重的…更多的Re in kor-apoe(Shl)，后面跟着其他的，如下所示；KOR-Apoe(shl)&gt；&gt；C3.KOR-Apoe(shl)&gt；C.KOR-Apoe(shl)&gt；B6.KOR-Apoe(shl).B6组动脉粥样硬化程度最重，其次为B6.KOR-Apoe(shl)&gt；C.KOR-Apoe(shl)&gt；&gt；C3.KOR-Apoe(shl)&gt；或=KOR-APOE(Shl)。然而，这一顺序与黄色瘤中的顺序不同，黄色瘤在KOR-APOE(Shl)中高度突出，而在B6、C.Kor-APOE(Shl)和C3.KORApoe(Shl)中轻微。然而，这一顺序与黄色瘤不同，黄色瘤在KOR-APOE(Shl)中高度突出，而在B6.Kor-APOE(Shl)、C.Kor-APOE(Shl)和C3.Kor-APOE(Shl)中轻微。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，这些遗传背景可能由脂代谢相关蛋白的多态性组成。我们发现，载脂蛋白A-I在各SHL株系中均降低，并且在B6.KOR-APOE(Shl)与其他被测株系之间具有多态。这种多态可能与B6中观察到的最严重的动脉粥样硬化有关。这种多态的结合很可能是由于表型差异的遗传背景所致。动脉粥样硬化杂志.2001；8(3)：71-9.较少

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