Detection of differentially expressed candidate genes for a fatty liver QTL on mouse chromosome 12.
Detection of differentially expressed candidate genes for a fatty liver QTL on mouse chromosome 12.
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DOI：
10.1186/s12863-016-0385-2
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发表时间：
2016-06-06
期刊：
影响因子：
2.9
通讯作者：
Horio F
中科院分区：
文献类型：
--
作者：
Kobayashi M;Suzuki M;Ohno T;Tsuzuki K;Taguchi C;Tateishi S;Kawada T;Kim YI;Murai A;Horio F
SMXA-5小鼠是高脂饮食诱导的脂肪肝的动物模型。在SM/J × SMXA-5的互交试验中，定位到位于第12染色体上的脂肪肝主效QTL Fl 1 sa。SMXA-5基因组由SM/J和A/J基因组组成，Fl 1 sa的A/J等位基因是脂肪肝易感性等位基因。在A/J-12 SM小鼠中证实了Fl 1 sa中脂肪肝相关基因的存在。本研究的目的是鉴定Fl 1 sa的候选基因，并研究所鉴定的基因是否影响脂质代谢。A/J-12 SM小鼠在高脂饮食喂养7周后，肝脏甘油三酯含量显著低于A/J小鼠。我们检测到A/J和A/J-12 SM同源小鼠之间的高脂饮食反应的肝脏脂质积累的差异。为了鉴定Fl 1 sa的候选基因，我们使用高脂饮食喂养的A/J-12 SM和A/J小鼠的肝脏进行了DNA微阵列分析。Fl 1 sa染色体区域的3个基因（Iah 1、Rrm 2、Prkd 1）的mRNA水平在菌株间存在显著差异。A/J-12 SM小鼠肝、肾和肺中Iah 1 mRNA水平显著高于A/J小鼠。A/J-12 SM小鼠肝脏Iah 1 mRNA水平是A/J小鼠的3.2倍。为了研究Iah 1对肝脏脂质代谢的影响，我们在小鼠肝癌Hepa 1 -6细胞中构建了稳定表达小鼠Iah 1蛋白的细胞系。在Hepa 1 -6细胞中过表达Iah 1可抑制在甘油三酯合成和脂质代谢中起重要作用的Cd 36和Dgat 2的mRNA水平。这些结果表明，12号染色体近端区域的Fl 1 sa影响高脂饮食小鼠的脂肪肝。Iah 1（isoamyl acetate-hydrolyzing esterase 1 homolog）被鉴定为Fl 1 sa的候选基因之一。这项研究表明，小鼠Iah 1基因调节肝脏中脂质代谢相关基因的表达。本文的在线版本（doi：10.1186/s12863-016-0385-2）包含补充材料，可供授权用户使用。
The SMXA-5 mouse is an animal model of high-fat diet-induced fatty liver. The major QTL for fatty liver, Fl1sa on chromosome 12, was identified in a SM/J × SMXA-5 intercross. The SMXA-5 genome consists of the SM/J and A/J genomes, and the A/J allele of Fl1sa is a fatty liver-susceptibility allele. The existence of the responsible genes for fatty liver within Fl1sa was confirmed in A/J-12SM consomic mice. The aim of this study was to identify candidate genes for Fl1sa, and to investigate whether the identified genes affect the lipid metabolism. A/J-12SM mice showed a significantly lower liver triglyceride content compared to A/J mice when fed the high-fat diet for 7 weeks. We detected differences in the accumulation of liver lipids in response to the high-fat diet between A/J and A/J-12SM consomic mice. To identify candidate genes for Fl1sa, we performed DNA microarray analysis using the livers of A/J-12SM and A/J mice fed the high-fat diet. The mRNA levels of three genes (Iah1, Rrm2, Prkd1) in the chromosomal region of Fl1sa were significantly different between the strains. Iah1 mRNA levels in the liver, kidney, and lung were significantly higher in A/J-12SM mice than in A/J mice. The hepatic Iah1 mRNA level in A/J-12SM mice was 3.2-fold higher than that in A/J mice. To examine the effect of Iah1 on hepatic lipid metabolism, we constructed a stable cell line expressing the mouse Iah1 protein in mouse hepatoma Hepa1-6 cells. Overexpression of Iah1 in Hepa1-6 cells suppressed the mRNA levels of Cd36 and Dgat2, which play important roles in triglyceride synthesis and lipid metabolism. These results demonstrated that Fl1sa on the proximal region of chromosome 12 affected fatty liver in mice on a high-fat diet. Iah1 (isoamyl acetate-hydrolyzing esterase 1 homolog) was identified as one of the candidate genes for Fl1sa. This study revealed that the mouse Iah1 gene regulated the expression of genes related to lipid metabolism in the liver. The online version of this article (doi:10.1186/s12863-016-0385-2) contains supplementary material, which is available to authorized users.