RAT AND MOUSE DIFFERENCES IN GENDER-PREDOMINANT EXPRESSION OF ORGANIC ANION TRANSPORTER (OAT1–3;SLC22A6–8) mRNA LEVELS

Abstract

ABSTRACT:Organic anion transporters (Oats) mediate the initial step of active renal excretion, specifically substrate uptake into proximal tubule cells. Despite extensive characterization of rat Oats, mouse Oat expression patterns are virtually unknown. This study was designed to identify basal expression patterns of mouse Oat1 (Slc22a6), Oat2 (Slc22a7), and Oat3 (Slc22a8) mRNA, compare these patterns with those in rat, and characterize postnatal development of mouse Oat mRNA. Tissues were collected from adult male and female 129J and C57BL/6 mice, and male and female C57BL/6 mice 0 to 40 days of age. Oat mRNA levels were determined by branched DNA signal amplification. Mouse Oat1 mRNA was primarily expressed in kidney of both strains, with male predominance. Mouse Oat2 mRNA levels were highest in kidney of both strains without gender predominance. In both strains, Oat3 mRNA was highest in kidney, and liver expression was male-predominant. However, only 129J mice had higher Oat3 mRNA levels in female kidney than in male kidney. During postnatal development, both Oat1 and Oat2 mRNA levels began to rise after 25 days of age. Oat3 mRNA levels rose gradually from birth through 40 days of age. Oat2 mRNA increased 30-fold during the first 40 days, whereas Oat1 and Oat3 increased about 2-fold. The most notable species differences in Oat mRNA expression were a lack of Oat2 female predominance in mouse kidney and a less dramatic Oat3 male predominance in mouse liver. With the exception of a significant species difference in Oat2 expression, many similarities were found between rat and mouse Oat mRNA levels.

Organic anion transporters: discovery, pharmacology, regulation and roles in pathophysiology

“…In such a case, it will be of interest to determine the mechanism supporting this organ-specific gender-dependent regulation. As alluded to above, renal Oat2 mRNA and protein was reported to be predominant in female rats and mice [56,[124][125][126][127]. Castration of male rats markedly increased renal rOat2 mRNA and protein [126,127], whereas ovariectomy in females resulted in a relatively weak reduction in rOat2 mRNA and protein [126].…”

“…In the first assessment, it was found that renal rOat1 mRNA levels were not different between male and female rats [124]. However, in several subsequent reports, male rats and mice exhibited higher mRNA levels [55,56,125]. Furthermore, a reduction in rOat1 mRNA via gonadectomy in males confirmed that this difference was due to greater androgen levels in males [125].…”

“…To date, Oat1 message has been detected in kidney, choroid plexus and olfactory mucosa [52][53][54]. In addition, a male-predominant mRNA expression has been reported for mouse kidney [55,56]. Further characterization of Oat1 in expression systems revealed that its transport properties mimicked that of the renal tertiary active transport system that had been observed in pre-cloning physiological studies [32,35,42].…”

“…Oat3/OAT3 mRNA has been identified in the blood-brain barrier endothelium, the lining of ventricles in the brain (choroid plexus) and kidney [52,[66][67][68]. Oat3 mRNA has also been found in rat liver, albeit at relatively low levels; however, hepatic expression was not observed in mice [52,56,64,65]. Although mice appear to exhibit a female predominance (2-fold) in renal expression of Oat3 message, no such difference is apparent in rat [55,64,65].…”

“…However, in addition to renal proximal tubular cells, Oat2 and Oat3 (Oat2cOat3) expression in hepatocytes has been reported [56,62,64]. One relevant question is whether renal dysfunction affects hepatic OAT expression; much like cholestasis influences renal OATs.…”