Disease relevance of SLC34A1

• Because hypercalciuria is a risk factor for nephrocalcinosis, we determined whether Npt2-/- mice form renal stones [1].
• Hereditary hypophosphatemic rickets with hypercalciuria is not caused by mutations in the Na/Pi cotransporter NPT2 gene [2].
• Three lambda phage clones encompassing the Na+/phosphate co-transporter (NaPi-3) gene and its 5' flanking region were isolated from a human genomic DNA library [3].
• However, unlike HHRH patients, Npt2(-/-) mice do not have rickets or osteomalacia [4].
• Intestinal epithelial cells from 19-day-old rat fetuses underwent electropermeabilization and were successfully transfected by three recombinant plasmids containing the cloned oncogenes from the human adenovirus type 2 early region E1A (SLC-11 cells) and polyoma virus and simian virus 40 large T tumor antigens (SLC-21 and SLC-41 cells) [5].

High impact information on SLC34A1

• Npt2 encodes a renal-specific, brush-border membrane Na+-phosphate (Pi) cotransporter that is expressed in the proximal tubule where the bulk of filtered Pi is reabsorbed [4].
• Our findings demonstrate that Npt2 is a major regulator of Pi homeostasis and necessary for normal skeletal development [4].
• At weaning, Npt2(-/-) mice have poorly developed trabecular bone and retarded secondary ossification, but, with increasing age, there is a dramatic reversal and eventual overcompensation of the skeletal phenotype [4].
• Two transcription start sites (at positions -9 and - 10 with respect to nucleotide 1 of NaPi-7 cDNA) and two polyadenylylation signals were identified in the Npt2 gene by primer extension, 5' and 3' rapid amplification of cDNA ends (RACE) [6].
• A 484-bp 5' flanking region of the Npt2 gene, comprising the CAAT box, TATA box, and exon 1, was cloned upstream of a luciferase reporter gene; this construct significantly stimulated luciferase gene expression, relative to controls, when transiently transfected into OK cells, a renal cell line expressing type II Na+ -Pi cotransporter activity [6].

Biological context of SLC34A1

• We have isolated two cDNA clones, NaPi-2 and NaPi-3, by screening rat kidney cortex and human kidney cortex cDNA libraries, respectively, for expression of sodium-dependent phosphate transport in Xenopus laevis oocytes [7].
• Linkage analysis indicated that the two NPT2 intragenic SNP as well as five microsatellite markers in the NPT2 gene region were not linked to HHRH in the Bedouin kindred [2].
• Mice deficient in the Npt2 gene were generated by targeted mutagenesis to define the role of Npt2 in the overall maintenance of Pi homeostasis, determine its impact on skeletal development, and clarify its relationship to autosomal disorders of renal Pi reabsorption in humans [4].
• We investigated whether a mutation of Phex (phosphate regulating gene homologies to endopeptidase on the X chromosome) has an effect on the expression level of type II sodium-dependent phosphate co-transporter (Npt2) in the developing teeth of the Hyp mouse [8].
• Transfection of fetal rat intestinal epithelial cells by viral oncogenes: establishment and characterization of the E1A-immortalized SLC-11 cell line [5].

Anatomical context of SLC34A1

• Two distinct renal Na-dependent Pi transporters, type IIa (NPT2a, SLC34A1) and type IIc (NPT2c, SLC34A3), are expressed in brush border membrane of proximal tubular cells where the bulk of filtered Pi is reabsorbed [9].
• Vitamin D responsiveness of the NaPi-3 promoter was also detected in COS-7 cells co-transfected with a human vitamin D receptor expression vector [3].
• Quantitative RT-PCR analyses revealed that the amount of Npt2b mRNA, an isoform of Npt2, in Hyp mouse tooth germs was significantly lower than that in wild-type mice, in both in vivo and in vitro experiments [8].
• It is concluded that immortal SLC-11 cells are a suitable model for studying the proliferation and differentiation of epithelial intestinal cells and analyzing cancer progression in the gastrointestinal tract [5].
• Inorganic phosphate (Pi) induced an inward current (IP) in Xenopus oocytes expressing the human renal Na+/Pi cotransporter NaPi-3 [10].

Associations of SLC34A1 with chemical compounds

• The onset of renal stones correlated developmentally with the absence of Npt2 expression and the expression of the genes responsible for the renal production (1alpha-hydroxylase) and catabolism (24-hydroxylase) of 1,25-dihydroxyvitamin D [1].
• Arsenate induced inward currents through NaPi-3 and decreased the apparent Km in measurements of IP [10].
• A T855C polymorphism resulting in a histidine to arginine transition was present in the open reading frame of NPT2 [11].

Other interactions of SLC34A1

• This review summarizes the characteristics of the solute carrier family SLC34 that is represented by the type ll Na/P(i)-cotransporters NaPi-lla (SLC34A1), NaPi-llb (SLC34A2) and NaPi-llc (SLC34A3) [12].
• Mutations in the gene encoding the human sodium-phosphate cotransporter (NPT2), causing reduced phosphate affinity and dominant-negative behavior, were described [13].
• These characteristics were different from those reported for hNaPi-3 and hPiT-1 in other systems [14].

Analytical, diagnostic and therapeutic context of SLC34A1

• SLC-11 cells were propagated for 21 months in culture (current passage, 76; doubling time, 17 hr) and were immortalized by E1A, as shown by RNA transfer blot (Northern blot) analysis and indirect immunofluorescence of the nuclear oncoproteins [5].
• Western blot analysis showed that NPT2 protein was increased in BBMVs from treated rats [15].
• The radiation hybrid results placed NPT2 between polymorphic microsatellite markers D5S498 and D5S469 [16].
• The chromosome locations of the rabbit (Oryctolagus cuniculus) Na+-phosphate cotransporter genes NPT1 and NPT2 were determined by fluorescence in situ hybridization [17].
• In Northern blots, using a cDNA probe related to human kidney-cortex Na/Pi-cotransport activity (NaPi-3), hybridization with a mRNA-species of 2.4-2.6 kb was obtained [18].

References