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猪硫酸盐转运蛋白基因的结构、组织及表达

Structure, organization and tissue expression of the pig and sulfate transporter genes.

作者信息

Barnes Samuel K, Eiby Yvonne A, Lee Soohyun, Lingwood Barbara E, Dawson Paul A

机构信息

Mater Research Institute, The University of Queensland, Woolloongabba, Queensland, Australia.

UQ Centre for Clinical Research, The University of Queensland, Brisbane, Queensland, Australia.

出版信息

Biochem Biophys Rep. 2017 Apr 13;10:215-223. doi: 10.1016/j.bbrep.2017.04.005. eCollection 2017 Jul.

Abstract

Sulfate is an obligate nutrient for fetal growth and development. In mice, the renal Slc13a1 sulfate transporter maintains high maternal circulating levels of sulfate in pregnancy, and the placental Slc13a4 sulfate transporter mediates sulfate supply to the fetus. Both of these genes have been linked to severe embryonal defects and fetal loss in mice. However, the clinical significance of and in human gestation is unknown. One approach towards understanding the potential involvement of these genes in human fetal pathologies is to use an animal model, such as the pig, which mimics the developmental trajectory of the human fetus more closely than the previously studied mouse models. In this study, we determined the tissue distribution of pig and mRNA, and compared the gene, cDNA and protein sequences of the pig, human and mouse homologues. Pig mRNA was expressed in the ileum and kidney, whereas pig mRNA was expressed in the placenta, choroid plexus and eye, which is similar to the tissue distribution in human and mouse. The pig gene contains 15 exons spread over 76 kb on chromosome 8, and encodes a protein of 594 amino acids that shares 90% and 85% identity with the human and mouse homologues, respectively. The pig gene is located approximately 11 Mb from on chromosome 8, and contains 16 exons spanning approximately 70 kb. The pig SLC13A4 protein contains 626 amino acids that share 91% and 90% identity with human and mouse homologues, respectively. The 5'-flanking region of contains several putative transcription factor binding sites, including GATA-1, GATA-3, Oct1 and TATA-box consensus sequences, which are conserved in the homologous human and mouse sequences. The 5'-flanking sequence of contains multiple putative transcription factor consensus sites, including GATA-1, TATA-box and Vitamin D responsive elements. This is the first report to define the tissue distribution of pig and mRNAs, and compare the gene, cDNA, 5'-flanking region and protein sequences to human and mouse.

摘要

硫酸盐是胎儿生长发育所必需的营养素。在小鼠中,肾脏的Slc13a1硫酸盐转运体在孕期维持母体循环中高浓度的硫酸盐水平,而胎盘的Slc13a4硫酸盐转运体介导硫酸盐向胎儿的供应。这两个基因都与小鼠严重的胚胎缺陷和胎儿丢失有关。然而,它们在人类妊娠中的临床意义尚不清楚。了解这些基因在人类胎儿病理中潜在作用的一种方法是使用动物模型,如猪,其比先前研究的小鼠模型更能模拟人类胎儿的发育轨迹。在本研究中,我们确定了猪Slc13a1和Slc13a4 mRNA的组织分布,并比较了猪、人和小鼠同源物的基因、cDNA和蛋白质序列。猪Slc13a1 mRNA在回肠和肾脏中表达,而猪Slc13a4 mRNA在胎盘、脉络丛和眼睛中表达,这与人和小鼠的组织分布相似。猪Slc13a1基因包含15个外显子,分布在8号染色体上76 kb的区域,编码一个594个氨基酸的蛋白质,与人及小鼠同源物的同源性分别为90%和85%。猪Slc13a4基因位于8号染色体上距离Slc13a1约11 Mb处,包含16个外显子,跨度约70 kb。猪SLC13A4蛋白包含626个氨基酸,与人及小鼠同源物的同源性分别为91%和90%。Slc13a1的5'侧翼区域包含几个假定的转录因子结合位点,包括GATA-1、GATA-3、Oct1和TATA框共有序列,这些序列在人类和小鼠的同源序列中是保守的。Slc13a4的5'侧翼序列包含多个假定的转录因子共有位点,包括GATA-1、TATA框和维生素D反应元件。这是第一份定义猪Slc13a1和Slc13a4 mRNAs组织分布,并将基因、cDNA、5'侧翼区域和蛋白质序列与人及小鼠进行比较的报告。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9220/5614667/d4494d326ce5/gr1.jpg

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