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1 Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas, United States
* To whom correspondence should be addressed. E-mail: michel.baum{at}utsouthwestern.edu.
Neonatal proximal tubules have substantively different passive paracellular transport properties than the adult proximal tubule, which results in a maturational change in the paracellular passive flux of ions. Neonatal proximal tubules have a higher PNa/PCl ratio and lower chloride and bicarbonate permeabilities than adult proximal tubules. Claudin isoform expression determines the permeability characteristics of the paracellular pathway. We compared the claudin isoforms present in the neonatal and adult kidney using RT-PCR to detect mRNA of claudin isoforms. Claudin-6, claudin-9 and claudin-13 were either not expressed or barely detectable in the adult mouse kidney using traditional PCR, but were expressed in the neonatal mouse kidney. Using real-time RT-PCR, we were able to detect a low level of claudin-6 mRNA expression in the adult kidney compared to the neonate, but claudin-9 and claudin-13 were only detected in the neonatal kidney. There was the same maturational decrease in these claudin proteins with western blot analysis. Immunohistochemistry showed high levels of expression of claudin-6 in neonatal proximal tubules, thick ascending limb, distal convoluted tubules and collecting ducts in a paracellular distribution but there was no expression of claudin-6 in the adult kidney. Using real-time RT-PCR claudin 6 and 9 mRNA were present in 1 day old proximal convoluted tubules and were virtually undetectable in proximal convoluted tubules from adults. Claudin 13 was not detectable. In summary, we have identified developmentally expressed claudin isoforms, claudin-6, claudin-9 and claudin-13. These paracellular proteins may play a role in the maturational changes in paracellular permeability.
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