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首页> 外文期刊>Journal of Lipid Research >Two novel quantitative trait loci on mouse chromosomes 6 and 4 independently and synergistically regulate plasma apoB levels.
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Two novel quantitative trait loci on mouse chromosomes 6 and 4 independently and synergistically regulate plasma apoB levels.

机译：小鼠染色体6和4上的两个新的定量性状基因座独立且协同调节血浆apoB水平。

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An elevated plasma apolipoprotein B (apoB) level is a strong predictor of atherosclerosis and coronary heart disease. Epidemiologic and family linkage studies have suggested a genetic basis for the wide variations of plasma apoB levels in the general population. Using a human apoB transgenic (HuBTg) mouse model, we have previously shown that hepatic apoB-100 secretion is a major determinant of the high and low plasma human apoB levels in HuBTg mice of the C57BL/6 (B6) and 129/Sv (129) strains, respectively. In the present article, we present the identification of two novel quantitative trait loci (QTL) as major regulators of plasma human apoB levels in the F(2) and N(2) (backcrossed) offspring (n = 572) derived from crosses between the B6 and 129 mouse strains. These loci were designated ApoB regulator genes (Abrg), because the gene products are likely to be involved in the regulation of plasma apoB levels either directly or indirectly. The first locus, designated Abrg1, was mapped to chromosome 6 in 8-week-old male and female mice with a combined logarithm of odds ratio (LOD) score of 14 at the D6Mit55 marker ( approximately 45.9 cM). Abrg1 contributed approximately 35% of the genetic variance. The second locus, designated Abrg2, was mapped to chromosome 4 with an LOD score of 8.6 in 8-week-old male mice but an LOD score of only 2.0 in 8-week-old female mice at the D4Mit27 marker ( approximately 35 cM). Abrg2 contributed approximately 26% of the genetic variance. Epistasis between Abrg1 and Abrg2 was detected and accounted for approximately 12% of the genetic variance. The combination of these two QTL has major effects (>70%) on the regulation of plasma human apoB levels in the tested population. In summary, we have identified two novel loci that have a major role in the regulation of plasma apoB levels and are likely to regulate the secretory pathway of apoB. The human orthologs for the Abrg loci are strong candidates for human disorders characterized by altered plasma apoB levels, such as FCHL and familial hypobetalipoproteinemia.
机译：血浆载脂蛋白B（apoB）水平升高是动脉粥样硬化和冠心病的有力预测指标。流行病学和家庭联系研究表明，一般人群中血浆apoB水平的广泛差异具有遗传基础。使用人类apoB转基因（HuBTg）小鼠模型，我们先前已经证明，肝脏apoB-100的分泌是C57BL / 6（B6）和129 / Sv的HuBTg小鼠中血浆人apoB高和低的主要决定因素（ 129）菌株。在本文中，我们介绍了两个新的定量性状基因座（QTL）的鉴定，它们是血浆人apoB水平的主要调节剂，其起源于F（2）和N（2）（回交）后代（n = 572），它们之间的杂交B6和129小鼠品系。这些基因座被称为ApoB调节基因（Abrg），因为这些基因产物可能直接或间接参与血浆apoB水平的调节。第一个基因座称为Abrg1，在8周龄的雄性和雌性小鼠中位于6号染色体上，在D6Mit55标记处的对数比（LOD）得分为14的对数（约45.9 cM）。 Abrg1贡献了大约35％的遗传变异。第二个基因座（称为Abrg2）在D4Mit27标记（约35 cM）处以8周龄雄性小鼠的LOD得分为8.6定位到4号染色体，而在8周龄雌性小鼠中的LOD得分仅为2.0。 。 Abrg2贡献了大约26％的遗传变异。检测到Abrg1和Abrg2之间的上位性，约占遗传变异的12％。这两个QTL的组合对受测人群中血浆人apoB水平的调节具有重大影响（> 70％）。总之，我们确定了两个新的基因座，它们在血浆apoB水平的调节中起主要作用，并且可能调节apoB的分泌途径。 Abrg基因座的人类直系同源物是针对以血浆apoB水平改变为特征的人类疾病（如FCHL和家族性低血脂蛋白血症）的强候选基因。

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