Structure, organization and tissue expression of the pig SLC13A1 and SLC13A4 sulfate transporter genes

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 SLC13A1 and SLC13A4 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 SLC13A1 and SLC13A4 mRNA, and compared the gene, cDNA and protein sequences of the pig, human and mouse homologues. Pig SLC13A1 mRNA was expressed in the ileum and kidney, whereas pig SLC13A4 mRNA was expressed in the placenta, choroid plexus and eye, which is similar to the tissue distribution in human and mouse. The pig SLC13A1 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 SLC13A4 gene is located approximately 11 Mb from SLC13A1 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 SLC13A1 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 SLC13A4 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 SLC13A1 and SLC13A4 mRNAs, and compare the gene, cDNA, 5’-flanking region and protein sequences to human and mouse.

Physiological and Pathological Functions of SLC26A6

“…Also, sulfate is an essential nutrient for the growth and development of fetus ( 124 ). However, the developing fetus have negligible capacity to generate sulfate from methionine and cysteine ( 125 , 126 ) and depends on sulfate supplied from maternal circulation via placental sulfate transporters ( 127 ). For human, several transporters have been detected in the placenta, which include SLC26A6 ( 21 ).…”

Early closure mechanisms of the ductus arteriosus in immature infants

“…Maternal serum sulphate levels are elevated in pregnancy because of the increase in activity of the sulphate transporter in the kidney and ileum (SLC3A1). In addition, a sulphate transporter in the placenta (SLC13A4) maintains the sulphate supply to the foetus 80 (Figure 4). Specific sulphotransferases transfer sulphate from 3′‐phosphoadenosine 5′‐phosphosulphates to multiple functionally essential molecules, including glucocorticoids, and the degree of sulphation may have important consequences in the immature foetus and infant (Figure 4).…”

Genome-wide association study and predictive ability for growth traits in Nellore cattle

“…This gene may exert some influence on birth weight, as reported by Sugimoto, Watanabe and Sugimoto (2012) in Holstein's calves. SLC13A4 gene express a protein that acts as sulfate carrier to the fetus during pregnancy (ZHANG et al, 2017), affecting the sulfate demand in circulation, which increases due to fetal need to growth and development (BARNES et al, 2017). The GBA3 gene was associated to hydrolyze beta-galactose and beta-glucose (DEKKER et al, 2011), and may be related with milk production, which influences calf weight after birth, since lactose represents 5% of milk composition and are a protein source for animal growth, coming from galactose (JENKINS, 1998).…”