Genetic variants in KDR transcriptional regulatory region affect promoter activity and intramuscular fat deposition in Erhualian pigs
Genetic variants in KDR transcriptional regulatory region affect promoter activity and intramuscular fat deposition in Erhualian pigs
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KDR转录调控区基因变异影响二花脸猪启动子活性和肌内脂肪沉积
DOI：
10.1111/age.12148
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发表时间：
2014-06-01
期刊：
影响因子：
2.4
通讯作者：
Chen, J.
中科院分区：
文献类型：
--
作者：
Fu, Y.;Sun, W.;Chen, J.
激酶插入结构域受体 (KDR) 是一种血管内皮生长因子 (VEGF) 受体，被广泛认为在介导 VEGF 诱导的血管生成反应中起主要作用。由于血管生成为脂肪细胞的生长和沉积提供氧气和营养，我们的目的是确定 KDR 基因中的启动子多态性是否对背最长肌中的肌内脂肪 (IMF) 沉积有影响。通过 DNA 库的比较测序，发现三个新的 SNP：c.-1316A>G、c.-1303C>T 和 c.-1108A>C 在高 IMF 含量组和低 IMF 含量组之间具有差异等位基因分布。这三个SNP完全连锁，在105头二花莲纯种猪和98头杜洛克x大白x约克夏（DxLxY）杂交猪中进行基因分型时，仅形成ACA或GTC单倍型。有趣的是，ACA 单倍型仅存在于二花莲猪中，而不存在于 DxLxY 猪中。使用基因表达分析或荧光素酶测定发现 ACA 启动子对于 KDR 转录具有比 GTC 类型更高的活性。定点突变分析表明c.-1316A>G是启动子活性改变的原因。此外，我们检测到两种血管内皮标志物 CD31（也称为 PECAM1）和 CD34 在 ACA/ACA 个体中表达较高。我们的结论是，ACA 启动子可能是通过促进更高的 KDR 基因表达和更多的血管网络来提高 IMF 含量的理想形式。
Kinase insert domain receptor (KDR), a vascular endothelial growth factor (VEGF) receptor, is widely regarded as having a principal role in mediating VEGF-induced responses in angiogenesis. As angiogenesis provides oxygen and nutrients for growth and deposition of adipose cells, our objective was to determine whether the promoter polymorphisms in the KDR gene have effects on intramuscular fat (IMF) deposition in the longissimus dorsi muscle. Three novel SNPs, c.-1316A>G, c.-1303C>T and c.-1108A>C, were revealed to have differential allele distribution between high- and low-IMF content groups by comparative sequencing of DNA pools. The three SNPs were completely linked, forming only ACA or GTC haplotypes when genotyped in 105 Erhualian purebred pigs and 98 DurocxLarge WhitexYorkshire (DxLxY) cross-bred pigs. It is interesting that the ACA haplotype is present exclusively in Erhualian pigs and not in DxLxY pigs. The ACA promoter was found to have higher activity than GTC type for KDR transcription using either gene expression analysis or luciferase assay. Site-direct mutation analysis demonstrated that c.-1316A>G is the causation of promoter activity alteration. Furthermore, we detected that CD31 (also known as PECAM1) and CD34, two blood vessel endothelial markers, expressed higher in ACA/ACA individuals. We concluded that the ACA promoter might be a desirable form for improving IMF content by promoting higher KDR gene expression and more blood vessel network.