Cloning, gene structure and dietary regulation of the type-IIc Na/Pi cotransporter in the mouse kidney
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We have demonstrated previously that the type-IIc Na/Pi cotransporter is a growth-related renal Na/Pi cotransporter that is highly expressed in kidney of the weaning rat. In the present study, we investigated type-IIc Na/Pi cotransporter function further by cloning the mouse gene and characterizing the corresponding protein. The mouse type-IIc transporter amino acid sequence shows a high degree of similarity to the human (86%) and rat (95%) type-IIc Na/Pi-cotransporters. The mouse gene contained 14 exons and mapped to chromosome 2. The DNA sequence upstream from exon 1 is GC rich. The upstream region does not contain an apparent TATA box, but does contain two dietary Pi-responsive elements, which are potential binding sites for the transcription factor µE3 (TFE3). Microinjection of mouse type-IIc cRNA into Xenopus oocytes demonstrated sodium-dependent Pi cotransport activity. The affinity for Pi was about 200 µM in 100 mM Na. Feeding adult mice fed a low-Pi diet increased the expression of type-IIc protein in the apical membrane of renal proximal tubular cells. Hybrid depletion studies suggested that the type-IIc transporter contributes to about 30% of Na/Pi cotransport in the kidney of adult mice fed a low-Pi diet. The present study suggests that the type-IIc Na/Pi cotransporter is a functional of renal Pi transporter in adult mice fed a low-Pi diet.
KeywordsPhosphate Transporter Weaning Regulation Proximal tubules
This work was supported by Grant 11557202 (K.M.) from the Ministry of Education, Science, Sports and Culture of Japan. We thank Kayo Yano, Ritsuko Saito, Keiko Shinohara, Noriko Yata and Ichiro Kaneko. The mouse osteoclast mRNA were a kind gift from Dr. Amano, Showa University, Tokyo, Japan. The nucleotide sequences reported in this paper have been submitted to the GenBank/EBI Data Bank with accession numbers AB054999 and AB080121-AB080134.
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