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Gene Review

Slc12a1  -  solute carrier family 12, member 1

Mus musculus

Synonyms: AI788571, BSC1, Bumetanide-sensitive sodium-(potassium)-chloride cotransporter 2, D630042G03Rik, Kidney-specific Na-K-Cl symporter, ...
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Disease relevance of Slc12a1

  • Cell proliferation under nonadhesive conditions was examined in anchorage-dependent mouse fibroblasts (3T3 and 3T6), in epithelial monkey kidney cells (BSC-1) and in four B16 melanoma cell variants that exhibit distinct metastatic properties [1].
  • Chronic metabolic acidosis enhances the ability of the medullary thick ascending limb (MTAL) to absorb NH(4)(+) at least in part by stimulating the mRNA and protein expression of BSC1/NKCC2, the MTAL apical Na(+)-K(+)(NH(4)(+))-2Cl(-) co-transporter [2].

High impact information on Slc12a1

  • Two Na-K-Cl cotransporters encoded by different genes have been identified in the mammalian kidney: BSC1/NKCC2 which localizes to the apical thick ascending limb of Henle and BSC2/NKCC1 which was isolated from a mouse IMCD cell line (mIMCD-3) but its localization has not been determined [3].
  • TAL cells exhibited furosemide-sensitive Na-K((NH4)+)-Cl cotransport activity and endogenously expressed the 5.0-kilobase Nkcc2 transcript [4].
  • Luciferase activity was 130-fold greater following transfection into TAL cells compared with transfection into cells that did not express Nkcc2 (NIH 3T3 fibroblasts) [4].
  • The murine Nkcc2/Slcl2a1 gene encodes a bumetanide-sensitive Na-K-Cl cotransporter that is expressed exclusively in the kidney in the thick ascending limb of the loop of Henle [4].
  • These results demonstrate that acid pH enhances the stability of BSC1 mRNA probably by activating pathways that act on the AU-rich 3'-UTR of BSC1 mRNA, which contributes to the renal response to metabolic acidosis [2].

Biological context of Slc12a1

  • Localization of the renal Na-K-Cl cotransporter gene (Slc12a1) on mouse chromosome 2 [5].
  • The C4 isoforms are generated by utilization of an alternative polyadenylation site located within the intron between exons 16 and 17 of the mBSC1 gene on chromosome 2; the resultant transcripts predict a truncated COOH terminus ending in a unique 55 amino acid sequence [6].
  • We conclude that a PKC, likely of the novel type, nPKC, seems to be involved in PMA-induced reduction of expressed BSC1 and/or its ion transport function [7].

Anatomical context of Slc12a1

  • The functional properties of alternatively spliced isoforms of the mouse apical Na+-K+-2Cl- cotransporter (mBSC1) were examined, using expression in Xenopus oocytes and measurement of 22Na+ or 86Rb+ uptake [8].
  • Attempts to follow the expression of BSC1 in plasma membranes with either immunoblotting or radio-methionine pulse-chase were unsuccessful [7].
  • A mouse monoclonal anti-alpha-tubulin antibody was used to investigate the disposition of the cytoskeletal microtubules of three tissue culture cell lines--J774 macrophages, BSC-1, and Vero cells--infected with the Brazil strain of Trypanosoma cruzi [9].

Associations of Slc12a1 with chemical compounds

  • In addition to a urea metabolite (II) formed by transformation of the cyanamide functionality, another highly polar metabolite was found in mouse urine and in BSC-1, MDCK, and other cell culture incubations of [14C]LY217896 [10].
  • Activating endogenous muscarinic receptors with 20 microM acetylcholine had no effect on expressed BSC1 fluxes [7].
  • However, long-term vasopressin infusion or thirsting of rats did not affect BSC-1 abundance [11].


  1. Multinucleation and inhibition of cytokinesis in suspended cells: reversal upon reattachment to a substrate. Ben-Ze'ev, A., Raz, A. Cell (1981) [Pubmed]
  2. Acid pH increases the stability of BSC1/NKCC2 mRNA in the medullary thick ascending limb. Karim, Z., Attmane-Elakeb, A., Sibella, V., Bichara, M. J. Am. Soc. Nephrol. (2003) [Pubmed]
  3. Expression of the mouse Na-K-2Cl cotransporter, mBSC2, in the terminal inner medullary collecting duct, the glomerular and extraglomerular mesangium, and the glomerular afferent arteriole. Kaplan, M.R., Plotkin, M.D., Brown, D., Hebert, S.C., Delpire, E. J. Clin. Invest. (1996) [Pubmed]
  4. Cloning and kidney cell-specific activity of the promoter of the murine renal Na-K-C1 cotransporter gene. Igarashi, P., Whyte, D.A., Li, K., Nagami, G.T. J. Biol. Chem. (1996) [Pubmed]
  5. Localization of the renal Na-K-Cl cotransporter gene (Slc12a1) on mouse chromosome 2. Quaggin, S.E., Payne, J.A., Forbush, B., Igarashi, P. Mamm. Genome (1995) [Pubmed]
  6. Isoforms of the Na-K-2Cl cotransporter in murine TAL I. Molecular characterization and intrarenal localization. Mount, D.B., Baekgaard, A., Hall, A.E., Plata, C., Xu, J., Beier, D.R., Gamba, G., Hebert, S.C. Am. J. Physiol. (1999) [Pubmed]
  7. Novel protein kinase C, nPKC, inhibition of murine bumetanide-sensitive Na+,K+,2Cl- cotransporter BSC1 in Xenopus oocyte. Baekgaard, A., Bindslev, N. Pflugers Arch. (1998) [Pubmed]
  8. Isoforms of the Na-K-2Cl cotransporter in murine TAL II. Functional characterization and activation by cAMP. Plata, C., Mount, D.B., Rubio, V., Hebert, S.C., Gamba, G. Am. J. Physiol. (1999) [Pubmed]
  9. A monoclonal antibody to alpha tubulin recognizes host cell and Trypanosoma cruzi tubulins. Paulin, J.J., Keith, C.H., Tarleton, R.L. J. Protozool. (1988) [Pubmed]
  10. Biotransformation of the antiviral agent 1,3,4-thiadiazol-2-ylcyanamide (LY217896) and characteristics of a mesoionic ribose metabolite. Ehlhardt, W.J., Wheeler, W.J., Breau, A.P., Chay, S.H., Birch, G.M. Drug Metab. Dispos. (1993) [Pubmed]
  11. Localization and regulation of the rat renal Na(+)-K(+)-2Cl- cotransporter, BSC-1. Ecelbarger, C.A., Terris, J., Hoyer, J.R., Nielsen, S., Wade, J.B., Knepper, M.A. Am. J. Physiol. (1996) [Pubmed]
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