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

• Slc12a2 is a direct target of two closely related homeobox proteins, Six1 and Six4 [6].
• The Slc12a2 gene encodes a widely expressed bumetanide-sensitive Na+-K+-2Cl- cotransporter that participates in various functions such as Cl- secretion and cell volume regulation [7].
• NKCC1-deficient (Nkcc1(-/-)) mice were used to examine its role in cardiac function and in the maintenance of blood pressure and vascular tone [8].
• Studies using pressure transducers in the femoral artery and left ventricle showed that anesthetized Nkcc1(-/-) mice have decreased mean arterial pressure and left ventricular pressure, whereas myocardial contraction parameters were not significantly different from those of Nkcc1(+/+) mice [8].

Anatomical context of Slc12a2

• Slc12a2 was highly expressed in the developing lung, gut, submandibular gland, tooth bud, and nasal epithelium [9].
• Slc12a2 expression was also observed in the developing central and peripheral nervous systems, including choroid plexus and trigeminal and dorsal root ganglia [9].
• In contrast, secretion of gastric acid in adult Nkcc1(-/-) stomachs and enterotoxin-stimulated fluid secretion in the intestine of suckling Nkcc1(-/-) mice were normal [10].
• In phasic portal vein smooth muscle from Nkcc1(-/-) mice, however, a sharp reduction in mechanical force was noted [8].

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].

References