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Am J Physiol Renal Physiol (August 15, 2001). doi:10.1152/ajprenal.0352.2000
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Articles in PresS, published online ahead of print August 15, 2001
Am J Physiol Renal Physiol, 10.1152/ajprenal.0352.2000
Submitted on December 28, 2000
Accepted on June 20, 2001

Expression of the Urate Transporter/Channel is Developmentally Regulated in Human Kidneys

Deborah P Hyink1, Joshua Z Rappoport1, Patricia D Wilson1, and Ruth G Abramson1*

1 Renal Division, Department of Medicine, Mount Sinai School of Medicine, New York, NY, USA

* To whom correspondence should be addressed. E-mail: raBRAMSON{at}smtplink.mssm.EDU.

Recombinant protein prepared from a cDNA cloned from rat kidney and its human homologue function as urate transporter/channels in lipid bilayers. Using the antibody (anti-uricase) that detected the rat cDNA clone, we now demonstrate that normal human kidneys contain an immunoreactive protein of identical size to that in rat kidney (36-37 kDa), presumably the human urate transporter/channel (hUAT). The amount of hUAT in kidney homogenates increases progressively from 13 weeks of gestation to the early postnatal period. During gestation hUAT expression is confined to the cytoplasm of proximal tubules of stage III/IV nephrons. However, at 1 year of age hUAT is primarily located subapically and within brush-borders of proximal tubules. Xenopus oocytes and differentiated A6 cells injected with cRNA and transfected with cDNA of hUAT, respectively, demonstrated a similar pattern: hUAT is not detected in oocytes but is abundantly expressed in cytoplasm and plasma membranes of A6 cells. These data imply that different developmental factors regulate the initiation of cytoplasmic hUAT expression and subsequent insertion into human proximal tubule brush-border membranes.




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