Identification of Soat1 as a quantitative trait locus gene on mouse chromosome 1 contributing to hyperlipidemia.
Identification of Soat1 as a quantitative trait locus gene on mouse chromosome 1 contributing to hyperlipidemia.
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DOI：
10.1371/journal.pone.0025344
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Shi W
中科院分区：
文献类型：
--
作者：
Lu Z;Yuan Z;Miyoshi T;Wang Q;Su Z;Chang CC;Shi W
我们先前在C57 BL/6（B6）和C3 H/HeJ（C3 H）载脂蛋白E-缺陷（apoE-/-）小鼠的杂交中发现了2个位于远端1号染色体上的紧密连锁的数量性状位点（QTL），这些位点导致血浆胆固醇和甘油三酯水平的主要变异。Soat 1编码甾醇O-酰基转移酶1，是位于近端连锁峰下方的功能候选基因。我们对Soat 1基因编码区进行了测序，并在B6和C3 H小鼠之间发现了4个单核苷酸多态性（SNP）。其中两个SNP导致氨基酸取代（Ile 147 Val和His 205 Tyr）。功能测定显示，尽管蛋白质表达水平相当，但相对于B6小鼠，C3 H小鼠腹腔巨噬细胞中Soat 1的酶活性增加。Soat 1的等位基因变体与B6.apoE−/−和C3H.apoE−/−小鼠之间的交叉中血浆胆固醇和甘油三酯水平的变化相关。C3 H等位基因的遗传导致血浆脂质水平显著高于B6等位基因的遗传。Soat 1变异体也与血浆酯化胆固醇水平的主要变化显著相关，但与游离胆固醇水平无关。在B6.apoE−/−小鼠中转基因表达C3 H Soat 1导致血浆胆固醇和甘油三酯水平升高。这些结果表明，Soat 1是一个QTL基因有助于高脂血症。
We previously identified two closely linked quantitative trait loci (QTL) on distal chromosome 1 contributing to major variations in plasma cholesterol and triglyceride levels in an intercross derived from C57BL/6 (B6) and C3H/HeJ (C3H) apolipoprotein E-deficient (apoE−/−) mice. Soat1, encoding sterol o-acyltransferase 1, is a functional candidate gene located underneath the proximal linkage peak. We sequenced the coding region of Soat1 and identified four single nucleotide polymorphisms (SNPs) between B6 and C3H mice. Two of the SNPs resulted in amino-acid substitutions (Ile147Val and His205Tyr). Functional assay revealed an increased enzyme activity of Soat1 in peritoneal macrophages of C3H mice relative to those of B6 mice despite comparable protein expression levels. Allelic variants of Soat1 were associated with variations in plasma cholesterol and triglyceride levels in an intercross between B6.apoE−/− and C3H.apoE−/− mice. Inheritance of the C3H allele resulted in significantly higher plasma lipid levels than inheritance of the B6 allele. Soat1 variants were also significantly linked to major variations in plasma esterified cholesterol levels but not with free cholesterol levels. Trangenic expression of C3H Soat1 in B6.apoE−/− mice resulted in elevations of plasma cholesterol and triglyceride levels. These results indicate that Soat1 is a QTL gene contributing to hyperlipidemia.
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影响因子：
64.8
作者：
通讯作者：
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DOI：
10.1016/s1388-1981(04)00025-3
发表时间：
2004-06-01
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作者：
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作者：
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