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

使用载脂蛋白E缺乏的自发性高脂血症小鼠寻找与动脉粥样硬化相关的基因。

• 批准号: 13558101
• 负责人: MATSUSHIMA Yoshibumi
• 金额: $ 5.95万
• 依托单位: Research Institute for Clinical Oncology, Saitama Cancer Center
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-13558101/
• 关键词: spontaneously hyperlipidemic (SHL) mice; Japanese wild mice; Apo E; atherosclerosis; hypercholesterolemia; xanthoma; congenic mice; 疾患モデル; SHLマウス; 機能性食品; C57BL; 6-Apoe^<-; ->; タウリン; アポリポプロテインE; 自然発症; 血清総コレステロール値

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

四种自发性高脂血症（SHL）小鼠：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）基因被破坏的日本野生小鼠（KOR）。这些小鼠（KOR-Apoe（shl））是超高胆固醇血症的并且发展为严重的黄色瘤，但是与ApoE敲除小鼠相比，它们的动脉粥样硬化相对轻微。首先，我们测试了这种区别是否是由于KOR-Apoe（shl）中Apoc 1和/或Apoc 2基因的额外突变。Southern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，我们建立了具有C57 BL/6、BALB/c和C3 H/He遗传背景的3个SHL小鼠品系，分别命名为C57 BL/6.KOR-Apoe（shl）（B6.KOR-Apoe（shl））、BALB/c.KOR-Apoe（shl）（C.KOR-Apoe（shl））和C3 H/He.KOR-Apoe（shl）（C3.KOR-Apoe（shl））。高胆固醇血症最严重 ...更多信息 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. KOR-Apoe（shl）中最严重，其次是其他：B6.KOR-Apoe（shl）>C.KOR-Apoe（shl）>>C3.KOR-Apoe（shl）>或=KOR-Apoe（shl）。然而，这一顺序与黄色瘤中的顺序不一致，黄色瘤在KOR-Apoe（shl）中高度突出，而在B6.KOR-Apoe（shl）、C.KOR-Apoe（shl）和C3. KORApoe（shl）中轻微。然而，这一顺序与黄色瘤中的顺序不一致，黄色瘤在KOR-Apoe（shl）中高度恶性，而在B6.KOR-Apoe（shl）、C.KOR-Apoe（shl）和C3.KOR-Apoe（shl）中轻度恶性。这些区别表明，每个表型的严重程度是由不同的遗传背景，这可能是由脂质代谢相关蛋白的多态性。我们发现载脂蛋白A-I在各SHL株中均降低，并在B6、KOR-Apoe（shl）与其他被检株之间存在多态性。该多态性可能与B6.KOR-Apoe（shl）中观察到的最严重的动脉粥样硬化有关。这是最有可能的，这种多态性的组合是由于遗传背景负责表型的区别。动脉粥样硬化血栓杂志.2001;8（3）：71-9.少

项目成果

松島 芳文(分担執筆): "モデル動物の作製と維持(森脇和郎, 米川博通, 山村研一編)"(株)エル・アイ・シー 浅田恵子. 1000 (2003)

松岛芳文（合着）：“模型动物的创建和维护（森胁一雄、米川弘道、山村健一编辑）”LIC Co., Ltd. Keiko Asada 1000 (2003)。

Four strains of spontaneously hyperlipidemic (SHL) mice : phenotypic distinctions determined by genetic backgrounds.

四种自发性高脂血症（SHL）小鼠品系：由遗传背景决定的表型差异。

• 发表时间: 2001
• 期刊: J Atheroscler Thromb. 8
• 作者: Matsushima Y;Sakurai T;Ohoka A;Ohnuki T;Tada N;Asoh Y;Tachibana M.
• 通讯作者: Tachibana M.

Y.Mathushima et al.: "Four Stra ins of Sporniancousiy Hperlipidemic(SHL)Mice : Phenotypic Disticitions Determined by Genetic Backgrounds"Journal of Atherosclerosis and Thrombosis.. Vol.8, No.3. 71-79 (2001)

Y.Mathushima 等：“孢子高脂血症 (SHL) 小鼠的四种品系：由遗传背景决定的表型特征”动脉粥样硬化和血栓形成杂志..第 8 卷，第 3 期。

コンジェニックSHLマウス

同类SHL小鼠

• 发表时间: 2002
• 期刊: The Lipid 13
• 作者: 松島 芳文

Yoshibumi Matsushima et al.: "EFFECTS OF TAURINE 0N SERUM CH0LESTEROL LEVELS ANDDEVELOPMENT 0F ATHEROSCLEROSIS IN SPONTANEOUSLY HYPERLIPIDAEMIC MICE"Clinical and Experimental Pharmacology and Physiology. 30(in press). (2003)

Yoshibumi Matsushima 等人：“牛磺酸 0N 血清胆固醇水平和发展 0F 动脉粥样硬化对自发性高脂血症小鼠的影响”临床和实验药理学和生理学。