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家猪载脂蛋白AI和CIII基因的特性分析

Characterization of the apolipoprotein AI and CIII genes in the domestic pig.

作者信息

Birchbauer A, Knipping G, Juritsch B, Aschauer H, Zechner R

机构信息

Institute of Medical Biochemistry, University of Graz, Austria.

出版信息

Genomics. 1993 Mar;15(3):643-52. doi: 10.1006/geno.1993.1119.

Abstract

The apolipoproteins (apo) AI and CIII are important constituents of triglyceride-rich lipoproteins and high-density lipoproteins. In humans, apo AI is believed to play an important protective role in the pathogenesis of arteriosclerosis, whereas apo CIII might be involved in the development of hypertriglyceridemia. Both human genes are located within a gene cluster on chromosome 11. Although the domestic pig has been widely used as an animal model in arteriosclerosis and lipid research, the porcine apolipoproteins genes are poorly characterized. In this report, the complete nucleotide sequences of the porcine apo AI and CIII genes are presented and we demonstrate, for the first time, apo CIII expression in the pig. Both genes are composed of four exons and three introns and resemble closely their human counterparts with regard to the transcriptional start sites, exon sizes, intron sizes, exon-intron borders, and the size of the intergenic region. The predicted pig apo AI is a protein of 241 amino acids, which is 2 amino acids shorter than human apo AI. The protein sequence was found to be very homologous to apo AI sequences in other mammalian species. Apo AI expression was detected on the mRNA level in porcine liver and intestine. The apo CIII gene encodes a protein with 73 amino acids, which is 6 amino acids shorter than human apo CIII. In contrast to the three isoforms of apo CIII found in humans, only one major isoform was detected in the pig. Presumably this isoform is unglycosylated. In addition to apo CIII expression in the liver and the intestine, a truncated form of apo CIII mRNA was also found in porcine kidney. Our studies demonstrate the presence of an apo CIII gene, an apo CIII mRNA, and an apo CIII protein in the pig and, therefore, exclude a hypothesized apo CIII deficiency in these animals.

摘要

载脂蛋白(apo)AI和CIII是富含甘油三酯的脂蛋白和高密度脂蛋白的重要组成成分。在人类中,apo AI被认为在动脉粥样硬化的发病机制中发挥重要的保护作用,而apo CIII可能参与高甘油三酯血症的发展。这两个人类基因都位于11号染色体上的一个基因簇内。尽管家猪已被广泛用作动脉粥样硬化和脂质研究的动物模型,但猪载脂蛋白基因的特征却知之甚少。在本报告中,我们给出了猪apo AI和CIII基因的完整核苷酸序列,并首次证明了猪体内apo CIII的表达。这两个基因均由四个外显子和三个内含子组成,在转录起始位点、外显子大小、内含子大小、外显子 - 内含子边界以及基因间区域的大小方面与人类对应基因极为相似。预测的猪apo AI是一种由241个氨基酸组成的蛋白质,比人类apo AI短2个氨基酸。发现该蛋白质序列与其他哺乳动物物种的apo AI序列高度同源。在猪的肝脏和肠道中检测到了apo AI在mRNA水平的表达。apo CIII基因编码一种由73个氨基酸组成的蛋白质,比人类apo CIII短6个氨基酸。与人类中发现的三种apo CIII同工型不同,在猪中仅检测到一种主要的同工型。推测这种同工型未被糖基化。除了在肝脏和肠道中表达apo CIII外,在猪肾脏中还发现了一种截短形式的apo CIII mRNA。我们的研究证明了猪体内存在apo CIII基因、apo CIII mRNA和apo CIII蛋白,因此排除了这些动物中假设的apo CIII缺陷。

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