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Gene Review

Slc12a2  -  solute carrier family 12, member 2

Mus musculus

Synonyms: 9330166H04Rik, Basolateral Na-K-Cl symporter, Bumetanide-sensitive sodium-(potassium)-chloride cotransporter 1, Nkcc1, Solute carrier family 12 member 2, ...
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High impact information on Slc12a2

  • We disrupted mouse Slc12a2 and report here that Slc12a2-/- mice are deaf and exhibit classic shaker/waltzer behaviour, indicative of inner-ear defects [1].
  • We show here that a (Na+)-(K+)-(2Cl-) cotransporter, NKCC1, is required for this Cl- current, in that ORNs deficient in Nkcc1 or incubated with an NKCC blocker (bumetanide) lack the Cl- current [2].
  • Consistent with this observation, we show that Slc12a2 is expressed in Sertoli cells, pachytene spermatocytes, and round spermatids isolated from wild-type animals [3].
  • Immunolocalization confirmed expression of mBSC2 protein on the basolateral surface of terminal IMCD segments and demonstrated expression in the papillary surface epithelium [4].
  • To directly test this possibility we studied the in vivo and in vitro functioning of acinar cells from the parotid glands of mice with targeted disruption of Na(+)/K(+)/2Cl(-) cotransporter isoform 1 (Nkcc1), the gene encoding the salivary Na(+)/K(+)/2Cl(-) cotransporter [5].

Biological context of Slc12a2


Anatomical context of Slc12a2


Associations of Slc12a2 with chemical compounds

  • When stimulated with phenylephrine, aortic smooth muscle from Nkcc1(+/+) and Nkcc1(-/-) mice exhibited no significant differences in maximum contractility and only moderate dose-response shifts [8].

Other interactions of Slc12a2

  • Tail-cuff measurements demonstrated that awake Nkcc1(-/-) mice had significantly lower systolic blood pressure than wild-type (Nkcc1(+/+)) mice (114.5 +/- 2.2 and 131.8 +/- 2.5 mmHg, respectively) [8].

Analytical, diagnostic and therapeutic context of Slc12a2

  • We examined the expression of Slc12a2 (NKCC1) transcripts in the developing mouse by Northern blot analysis and in situ hybridization (ISH) using riboprobes transcribed from a cDNA encoding the transmembrane domain of human Slc12a2 [9].
  • Western blot analysis with affinity-purified anti-mBSC2 showed a protein doublet of 140 and 150 kD which was most abundant in the renal papilla but also seen in cortex and outer medulla [4].
  • We used in situ hybridization and immunocytochemistry with polyclonal antibodies against the mouse bumetanide-sensitive Na(+)-K(+)-2Cl- cotransporter (mBSC2) to determine the location of this cotransporter in rat brain [11].


  1. Deafness and imbalance associated with inactivation of the secretory Na-K-2Cl co-transporter. Delpire, E., Lu, J., England, R., Dull, C., Thorne, T. Nat. Genet. (1999) [Pubmed]
  2. Mechanism of the excitatory Cl- response in mouse olfactory receptor neurons. Reisert, J., Lai, J., Yau, K.W., Bradley, J. Neuron (2005) [Pubmed]
  3. Failure of spermatogenesis in mouse lines deficient in the Na(+)-K(+)-2Cl(-) cotransporter. Pace, A.J., Lee, E., Athirakul, K., Coffman, T.M., O'Brien, D.A., Koller, B.H. J. Clin. Invest. (2000) [Pubmed]
  4. 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]
  5. Severe impairment of salivation in Na+/K+/2Cl- cotransporter (NKCC1)-deficient mice. Evans, R.L., Park, K., Turner, R.J., Watson, G.E., Nguyen, H.V., Dennett, M.R., Hand, A.R., Flagella, M., Shull, G.E., Melvin, J.E. J. Biol. Chem. (2000) [Pubmed]
  6. Slc12a2 is a direct target of two closely related homeobox proteins, Six1 and Six4. Ando, Z., Sato, S., Ikeda, K., Kawakami, K. FEBS J. (2005) [Pubmed]
  7. Partial cloning and characterization of Slc12a2: the gene encoding the secretory Na+-K+-2Cl- cotransporter. Randall, J., Thorne, T., Delpire, E. Am. J. Physiol. (1997) [Pubmed]
  8. Decreased blood pressure and vascular smooth muscle tone in mice lacking basolateral Na(+)-K(+)-2Cl(-) cotransporter. Meyer, J.W., Flagella, M., Sutliff, R.L., Lorenz, J.N., Nieman, M.L., Weber, C.S., Paul, R.J., Shull, G.E. Am. J. Physiol. Heart Circ. Physiol. (2002) [Pubmed]
  9. Expression of the basolateral Na-K-Cl cotransporter during mouse nephrogenesis and embryonic development. Vanden Heuvel, G.B., Payne, J.A., Igarashi, P., Forbush, B. Gene Expr. Patterns (2006) [Pubmed]
  10. Mice lacking the basolateral Na-K-2Cl cotransporter have impaired epithelial chloride secretion and are profoundly deaf. Flagella, M., Clarke, L.L., Miller, M.L., Erway, L.C., Giannella, R.A., Andringa, A., Gawenis, L.R., Kramer, J., Duffy, J.J., Doetschman, T., Lorenz, J.N., Yamoah, E.N., Cardell, E.L., Shull, G.E. J. Biol. Chem. (1999) [Pubmed]
  11. Expression of the Na(+)-K(+)-2Cl- cotransporter BSC2 in the nervous system. Plotkin, M.D., Kaplan, M.R., Peterson, L.N., Gullans, S.R., Hebert, S.C., Delpire, E. Am. J. Physiol. (1997) [Pubmed]
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