Genetic dissection of the fatty liver QTL Fl1sa by using congenic mice and identification of candidate genes in the liver and epididymal fat.
Genetic dissection of the fatty liver QTL Fl1sa by using congenic mice and identification of candidate genes in the liver and epididymal fat.
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DOI：
10.1186/s12863-016-0453-7
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发表时间：
2016-11-17
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：
Suzuki M;Kobayashi M;Ohno T;Kanamori S;Tateishi S;Murai A;Horio F
非酒精性脂肪性肝病（NAFLD）是一种多因素疾病，由环境和遗传因素之间的相互作用引起。SMXA-5小鼠是由SM/J和A/J品系建立的高脂饮食诱导的脂肪肝模型。我们以前已经确定了Fl 1 sa，脂肪肝的数量性状位点（QTL）的SMXA-5小鼠的12号染色体（着丝粒-53.06 Mb）。然而，含有Fl 1 sa的染色体区域太宽。本研究的目的是缩小Fl 1 sa区域的遗传解剖使用新的同类小鼠，并确定缩小的Fl 1 sa区域内的候选基因。我们从亲本A/J-12 SM和A/J株中建立了两个同源株R2和R3。R_2和R_3株的12号染色体的着丝粒间距分别为29.20 -46.75 Mb和29.20-46.75 Mb。R2和R3小鼠的肝脏甘油三酯含量显著低于高脂饮食喂养7周的A/J小鼠。这一结果表明，至少有一个负责脂肪肝的基因存在于两个染色体区域内-29.20 Mb（R2）和29.20-46.75 Mb（R3）。我们发现，肝脏甘油三酯积累与附睾脂肪重量之间的父母和同类株呈负相关。因此，肝脏中的异位脂肪积聚可能是由于肝脏和附睾脂肪之间的器官-器官相互作用。为了鉴定Fl 1 sa中的候选基因，我们使用高脂饮食喂养7周的A/J和A/J-12 SM小鼠的肝脏和附睾脂肪进行了DNA微阵列分析。在附睾脂肪中，Zfp 125（R2）和Nrcam（R3）的mRNA水平在A/J-12 SM小鼠中与A/J小鼠中显著不同。在肝脏中，Iah 1（R2）和Rrm 2（R2）的mRNA水平在A/J-12 SM小鼠与A/J小鼠中有显著差异。在这项研究中，使用同源小鼠分析，我们缩小了染色体区域包含Fl 1 sa的小鼠染色体12的两个区域。然后，我们确定了Fl 1 sa中的4个候选基因：来自肝脏的Iah 1和Rrm 2以及来自附睾脂肪的Zfp 125和Nrcam。本文的在线版本（doi：10.1186/s12863-016-0453-7）包含补充材料，可供授权用户使用。
Nonalcoholic fatty liver disease (NAFLD) is a multifactorial disease caused by interactions between environmental and genetic factors. The SMXA-5 mouse is a high-fat diet-induced fatty liver model established from SM/J and A/J strains. We have previously identified Fl1sa, a quantitative trait locus (QTL) for fatty liver on chromosome 12 (centromere-53.06 Mb) of SMXA-5 mice. However, the chromosomal region containing Fl1sa was too broad. The aim of this study was to narrow the Fl1sa region by genetic dissection using novel congenic mice and to identify candidate genes within the narrowed Fl1sa region. We established two congenic strains, R2 and R3, from parental A/J-12SM and A/J strains. R2 and R3 strains have genomic intervals of centromere-29.20 Mb and 29.20–46.75 Mb of chromosome 12 derived from SM/J, respectively. Liver triglyceride content in R2 and R3 mice was significantly lower than that in A/J mice fed with a high-fat diet for 7 weeks. This result suggests that at least one of the genes responsible for fatty liver exists within the two chromosomal regions centromere-29.20 Mb (R2) and 29.20–46.75 Mb (R3). We found that liver triglyceride accumulation is inversely correlated with epididymal fat weight among the parental and congenic strains. Therefore, the ectopic fat accumulation in the liver may be due to organ-organ interactions between the liver and epididymal fat. To identify candidate genes in Fl1sa, we performed a DNA microarray analysis using the liver and epididymal fat in A/J and A/J-12SM mice fed with a high-fat diet for 7 weeks. In epididymal fat, mRNA levels of Zfp125 (in R2) and Nrcam (in R3) were significantly different in A/J-12SM mice from those in A/J mice. In the liver, mRNA levels of Iah1 (in R2) and Rrm2 (in R2) were significantly different in A/J-12SM mice from those in A/J mice. In this study, using congenic mice analysis, we narrowed the chromosomal region containing Fl1sa to two regions of mouse chromosome 12. We then identified 4 candidate genes in Fl1sa: Iah1 and Rrm2 from the liver and Zfp125 and Nrcam from epididymal fat. The online version of this article (doi:10.1186/s12863-016-0453-7) contains supplementary material, which is available to authorized users.
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DOI：
10.1097/mco.0b013e3283547157
发表时间：
2012-07
影响因子：
3.1
作者：
Schugar RC;Crawford PA
通讯作者：
Crawford PA
影响因子：
3.5
作者：
Giorgi, S;Polimeni, M;Bouché, M
通讯作者：
Bouché, M
影响因子：
13.5
作者：
Birkenfeld, Andreas L.;Shulman, Gerald I.
通讯作者：
Shulman, Gerald I.
影响因子：
2.9
作者：
Kobayashi M;Suzuki M;Ohno T;Tsuzuki K;Taguchi C;Tateishi S;Kawada T;Kim YI;Murai A;Horio F
通讯作者：
Horio F
影响因子：
6.5
作者：
Kumazawa, Mayumi;Kobayashi, Misato;Horio, Fumihiko
通讯作者：
Horio, Fumihiko