Gene Symbol: Slc12a1
Description: solute carrier family 12, member 1
Alias: AI788571, D630042G03Rik, Nkcc2, mBSC1, urehr3, solute carrier family 12 member 1, BSC1, bumetanide-sensitive cotransporter type 1, bumetanide-sensitive sodium-(potassium)-chloride cotransporter 2, kidney-specific Na-K-Cl symporter
Species: mouse
Products:     Slc12a1

Top Publications

  1. Fraser S, Gimenez I, Cook N, Jennings I, Katerelos M, Katsis F, et al. Regulation of the renal-specific Na+-K+-2Cl- co-transporter NKCC2 by AMP-activated protein kinase (AMPK). Biochem J. 2007;405:85-93 pubmed
    The renal-specific NKCC2 (Na+-K+-2Cl- co-transporter 2) is regulated by changes in phosphorylation state, however, the phosphorylation sites and kinases responsible have not been fully elucidated...
  2. Kemter E, Rathkolb B, Bankir L, Schrewe A, Hans W, Landbrecht C, et al. Mutation of the Na(+)-K(+)-2Cl(-) cotransporter NKCC2 in mice is associated with severe polyuria and a urea-selective concentrating defect without hyperreninemia. Am J Physiol Renal Physiol. 2010;298:F1405-15 pubmed publisher
    ..In humans, loss-of-function mutations of the solute carrier family 12 member 1 gene (SLC12A1), coding for NKCC2, cause type I Bartter syndrome, which is characterized by prenatal ..
  3. Basta J, Robbins L, Denner D, Kolar G, Rauchman M. A Sall1-NuRD interaction regulates multipotent nephron progenitors and is required for loop of Henle formation. Development. 2017;144:3080-3094 pubmed publisher
    ..These global changes in gene expression were accompanied by a significant decrease in THP-, NKCC2- and AQP1-positive loop of Henle nephron segments in mutant ?SRM kidneys...
  4. Simon D, Karet F, Hamdan J, DiPietro A, Sanjad S, Lifton R. Bartter's syndrome, hypokalaemic alkalosis with hypercalciuria, is caused by mutations in the Na-K-2Cl cotransporter NKCC2. Nat Genet. 1996;13:183-8 pubmed
    ..We demonstrate linkage of Bartter's syndrome to the renal Na-K-2Cl cotransporter gene NKCC2, and identify frameshift or non-conservative missense mutations for this gene that co-segregate with the disease...
  5. Reiche J, Theilig F, Rafiqi F, Carlo A, Militz D, Mutig K, et al. SORLA/SORL1 functionally interacts with SPAK to control renal activation of Na(+)-K(+)-Cl(-) cotransporter 2. Mol Cell Biol. 2010;30:3027-37 pubmed publisher
    ..cellular defect was correlated with an inability of the TAL to phosphorylate Na(+)-K(+)-Cl(-) cotransporter 2 (NKCC2), the major sodium transporter in the distal nephron...
  6. Richardson C, Sakamoto K, de los Heros P, Deak M, Campbell D, Prescott A, et al. Regulation of the NKCC2 ion cotransporter by SPAK-OSR1-dependent and -independent pathways. J Cell Sci. 2011;124:789-800 pubmed publisher
    ..Here, we study the regulation of the NKCC2 (SLC12A1) ion cotransporter that contributes towards ~25% of renal salt re-absorption and is inhibited by loop-diuretic ..
  7. Hao S, Bellner L, Ferreri N. NKCC2A and NFAT5 regulate renal TNF production induced by hypertonic NaCl intake. Am J Physiol Renal Physiol. 2013;304:F533-42 pubmed publisher
    ..hypertonic NaCl intake increases renal TNF production by a pathway involving the Na(+)-K(+)-2Cl(-) cotransporter (NKCC2). A 2...
  8. Oppermann M, Mizel D, Kim S, Chen L, Faulhaber Walter R, Huang Y, et al. Renal function in mice with targeted disruption of the A isoform of the Na-K-2Cl co-transporter. J Am Soc Nephrol. 2007;18:440-8 pubmed
    Three different full-length splice isoforms of the Na-K-2Cl co-transporter (NKCC2/BSC1) are expressed along the thick ascending limb of Henle (TAL), designated NKCC2A, NKCC2B, and NKCC2F...
  9. Yu G, Cheng M, Wang W, Zhao R, Liu Z. Involvement of WNK1-mediated potassium channels in the sexual dimorphism of blood pressure. Biochem Biophys Res Commun. 2017;485:255-260 pubmed publisher
    ..while large-conductance Ca2+-activated K+ (BK) channel and Na-K-2Cl cotransporter (NKCC2) as well as the upstream regulator with-no-lysine kinase 1 (WNK1) enhanced in female mice under normal condition...

More Information


  1. Alshahrani S, Almutairi M, Kursan S, Dias Junior E, Almiahuob M, Aguilar Bryan L, et al. Increased Slc12a1 expression in β-cells and improved glucose disposal in Slc12a2 heterozygous mice. J Endocrinol. 2015;227:153-65 pubmed publisher
    The products of the Slc12a1 and Slc12a2 genes, commonly known as Na(+)-dependent K(+)2Cl(-) co-transporters NKCC2 and NKCC1, respectively, are the targets for the diuretic bumetanide...
  2. Delaloy C, Hadchouel J, Imbert Teboul M, Clemessy M, Houot A, Jeunemaitre X. Cardiovascular expression of the mouse WNK1 gene during development and adulthood revealed by a BAC reporter assay. Am J Pathol. 2006;169:105-18 pubmed
    ..Despite this limitation, this transgenic model is a potentially valuable tool for the analysis of spatial and temporal aspects of WNK1 expression and regulation. ..
  3. Gillen C, Brill S, Payne J, Forbush B. Molecular cloning and functional expression of the K-Cl cotransporter from rabbit, rat, and human. A new member of the cation-chloride cotransporter family. J Biol Chem. 1996;271:16237-44 pubmed
    ..These data demonstrate that the KCC1 cDNAs encode a widely expressed K-Cl cotransporter with the characteristics of the K-Cl transporter that has been characterized in red cells...
  4. Pietilä I, Ellwanger K, Railo A, Jokela T, Barrantes I, Shan J, et al. Secreted Wnt antagonist Dickkopf-1 controls kidney papilla development coordinated by Wnt-7b signalling. Dev Biol. 2011;353:50-60 pubmed publisher
    ..Since Pax8Cre-induced Dkk1 deficiency reduced marker gene expression, Scnn1b in the collecting duct and Slc12a1 in the loop of Henle, these results together with the extended papilla phenotype are likely reasons for the ..
  5. Benziane B, Demaretz S, Defontaine N, Zaarour N, Cheval L, Bourgeois S, et al. NKCC2 surface expression in mammalian cells: down-regulation by novel interaction with aldolase B. J Biol Chem. 2007;282:33817-30 pubmed
    Apical bumetanide-sensitive Na(+)-K(+)-2Cl(-) co-transporter, termed NKCC2, is the major salt transport pathway in kidney thick ascending limb. NKCC2 surface expression is subject to regulation by intracellular protein trafficking...
  6. Narlis M, Grote D, Gaitan Y, Boualia S, Bouchard M. Pax2 and pax8 regulate branching morphogenesis and nephron differentiation in the developing kidney. J Am Soc Nephrol. 2007;18:1121-9 pubmed
    ..Together, these results demonstrate a crucial role for Pax2 and Pax8 in nephron differentiation and branching morphogenesis of the metanephros. ..
  7. Liu Z, Xie J, Wu T, Truong T, Auchus R, Huang C. Downregulation of NCC and NKCC2 cotransporters by kidney-specific WNK1 revealed by gene disruption and transgenic mouse models. Hum Mol Genet. 2011;20:855-66 pubmed publisher
    ..revealed reduced surface expression of total and phosphorylated NCC and the Na(+)-K(+)-2Cl(-) cotransporter NKCC2 in the distal convoluted tubule and the thick ascending limb of Henle's loop, respectively...
  8. Wu J, Liu X, Lai G, Yang X, Wang L, Zhao Y. Synergistical effect of 20-HETE and high salt on NKCC2 protein and blood pressure via ubiquitin-proteasome pathway. Hum Genet. 2013;132:179-87 pubmed publisher
    ..whereby diverse levels of 20-HETE interact with dietary salt on Na(+)-K(+)-2Cl(-) cotransporter, isoform 2 (NKCC2) in the kidneys of the transgenic and wild-type mice with high salt intake...
  9. Oppermann M, Mizel D, Huang G, Li C, Deng C, Theilig F, et al. Macula densa control of renin secretion and preglomerular resistance in mice with selective deletion of the B isoform of the Na,K,2Cl co-transporter. J Am Soc Nephrol. 2006;17:2143-52 pubmed
    Na,K,2Cl co-transporter (NKCC2), the primary NaCl uptake pathway in the thick ascending limb of Henle, is expressed in three different full-length splice variants, called NKCC2F, NKCC2A, and NKCC2B...
  10. Zaarour N, Demaretz S, Defontaine N, Zhu Y, Laghmani K. Multiple evolutionarily conserved Di-leucine like motifs in the carboxyl terminus control the anterograde trafficking of NKCC2. J Biol Chem. 2012;287:42642-53 pubmed publisher
    Mutations in the apical Na-K-2Cl co-transporter, NKCC2, cause type I Bartter syndrome, a life-threatening kidney disease. Yet the mechanisms underlying the regulation of NKCC2 trafficking in renal cells are scarcely known...
  11. Rossier B, Staub O, Hummler E. Genetic dissection of sodium and potassium transport along the aldosterone-sensitive distal nephron: importance in the control of blood pressure and hypertension. FEBS Lett. 2013;587:1929-41 pubmed publisher
    ..This will allow to design rational strategies for the treatment of hypertension and for the development of the next generation of diuretics. ..
  12. Nagalakshmi V, Ren Q, Pugh M, Valerius M, McMahon A, Yu J. Dicer regulates the development of nephrogenic and ureteric compartments in the mammalian kidney. Kidney Int. 2011;79:317-30 pubmed publisher
    ..Furthermore, an understanding of miRNA action may provide new insights into the etiology and pathogenesis of renal cyst-based kidney disease. ..
  13. Xue H, Zhang Z, Li X, Sun H, Kang Q, Wu B, et al. Localization and vasopressin regulation of the Na?-K?-2Cl? cotransporter in the distal colonic epithelium. World J Gastroenterol. 2014;20:4692-701 pubmed publisher
    To investigate whether Na(+)-K(+)-2Cl(-) cotransporter (NKCC2) is expressed in the mouse distal colonic epithelia and whether it is regulated by vasopressin in the colon...
  14. Pathak B, Shaughnessy J, Meneton P, Greeb J, Shull G, Jenkins N, et al. Mouse chromosomal location of three epithelial sodium channel subunit genes and an apical sodium chloride cotransporter gene. Genomics. 1996;33:124-7 pubmed
    ..gamma subunit genes, Scnn1a, Scnn1b, and Scnn1g, and the thiazide-sensitive sodium chloride cotransporter gene, Slc12a1, have been mapped in the mouse using an interspecific backcross panel...
  15. Lin S, Yu I, Jiang S, Lin S, Chu P, Chen A, et al. Impaired phosphorylation of Na(+)-K(+)-2Cl(-) cotransporter by oxidative stress-responsive kinase-1 deficiency manifests hypotension and Bartter-like syndrome. Proc Natl Acad Sci U S A. 2011;108:17538-43 pubmed publisher
    Na(+)-K(+)-2Cl(-) cotransporters (NKCCs), including NKCC1 and renal-specific NKCC2, and the Na(+)-Cl(-) cotransporter (NCC) play pivotal roles in the regulation of blood pressure (BP) and renal NaCl reabsorption...
  16. Tran U, Zakin L, Schweickert A, Agrawal R, D ger R, Blum M, et al. The RNA-binding protein bicaudal C regulates polycystin 2 in the kidney by antagonizing miR-17 activity. Development. 2010;137:1107-16 pubmed publisher
    ..Based on these data, we propose that the kidney phenotype in Bicc1(-/-) mutant mice is caused by dysregulation of a microRNA-based translational control mechanism...
  17. Aigner B, Rathkolb B, Herbach N, Kemter E, Schessl C, Klaften M, et al. Screening for increased plasma urea levels in a large-scale ENU mouse mutagenesis project reveals kidney disease models. Am J Physiol Renal Physiol. 2007;292:F1560-7 pubmed
  18. Castrop H, Schnermann J. Isoforms of renal Na-K-2Cl cotransporter NKCC2: expression and functional significance. Am J Physiol Renal Physiol. 2008;295:F859-66 pubmed publisher
    ..Although NKCC2 is encoded by a single gene (Slc12a1), differential splicing of the NKCC2 pre-mRNA results in the formation of several alternate transcripts...
  19. Paliege A, Roeschel T, Neymeyer H, Seidel S, Kahl T, Daigeler A, et al. Group VIA phospholipase A2 is a target for vasopressin signaling in the thick ascending limb. Am J Physiol Renal Physiol. 2012;302:F865-74 pubmed publisher
    Na(+)-K(+)-2Cl(-) cotransporter (NKCC2)-mediated NaCl reabsorption in the thick ascending limb (TAL) is stimulated by AVP via V2 receptor/PKA/cAMP signaling...
  20. Zhang Y, Sun Y, Ding G, Huang S, Zhang A, Jia Z. Inhibition of Mitochondrial Complex-1 Prevents the Downregulation of NKCC2 and ENaCα in Obstructive Kidney Disease. Sci Rep. 2015;5:12480 pubmed publisher
    ..obstruction (UUO) for 7 days, a global reduction of sodium transporters, including NHE3, α-Na-K-ATPase, NCC, NKCC2, p-NKCC2, ENaCα, and ENaCγ, was observed, as determined via qRT-PCR and/or Western blotting...
  21. Kosfeld A, Brand F, Weiss A, Kreuzer M, Goerk M, Martens H, et al. Mutations in the leukemia inhibitory factor receptor (LIFR) gene and Lifr deficiency cause urinary tract malformations. Hum Mol Genet. 2017;26:1716-1731 pubmed publisher
    ..3% of CAKUT patients, and provide evidence that Lifr deficiency and deactivating LIFR mutations cause highly similar anomalies of the urogenital tract in mice and humans. ..
  22. Jeong H, Jeon U, Koo B, Kim W, Im S, Shin J, et al. Inactivation of Notch signaling in the renal collecting duct causes nephrogenic diabetes insipidus in mice. J Clin Invest. 2009;119:3290-300 pubmed publisher
  23. Plata C, Mount D, Rubio V, Hebert S, Gamba G. Isoforms of the Na-K-2Cl cotransporter in murine TAL II. Functional characterization and activation by cAMP. Am J Physiol. 1999;276:F359-66 pubmed
    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...
  24. Caceres P, Mendez M, Haque M, Ortiz P. Vesicle-associated Membrane Protein 3 (VAMP3) Mediates Constitutive Trafficking of the Renal Co-transporter NKCC2 in Thick Ascending Limbs: ROLE IN RENAL FUNCTION AND BLOOD PRESSURE. J Biol Chem. 2016;291:22063-22073 pubmed
    ..ascending limb (TAL) reabsorb NaCl via the apical Na+/K+/2Cl- co-transporter NKCC2. Trafficking of NKCC2 to the apical surface regulates NKCC2-mediated NaCl absorption and blood pressure...
  25. Quaggin S, Payne J, Forbush B, Igarashi P. Localization of the renal Na-K-Cl cotransporter gene (Slc12a1) on mouse chromosome 2. Mamm Genome. 1995;6:557-8 pubmed
  26. Park H, Curry J, McCormick J. Regulation of NKCC2 activity by inhibitory SPAK isoforms: KS-SPAK is a more potent inhibitor than SPAK2. Am J Physiol Renal Physiol. 2013;305:F1687-96 pubmed publisher
    The cation cotransporters Na(+)-K(+)-2Cl(-) cotransporter 1 and 2 (NKCC1 and NKCC2) and Na(+)-Cl cotransporter (NCC) are phosphorylated and activated by the kinases Ste20-related proline alanine-rich kinase (SPAK) and oxidative stress-..
  27. Zhang J, Rudemiller N, Patel M, Karlovich N, Wu M, McDonough A, et al. Interleukin-1 Receptor Activation Potentiates Salt Reabsorption in Angiotensin II-Induced Hypertension via the NKCC2 Co-transporter in the Nephron. Cell Metab. 2016;23:360-8 pubmed publisher
    ..deficiency or blockade limits blood pressure elevation in this model by mitigating sodium reabsorption via the NKCC2 co-transporter in the nephron...
  28. Vanden Heuvel G, Payne J, Igarashi P, Forbush B. Expression of the basolateral Na-K-Cl cotransporter during mouse nephrogenesis and embryonic development. Gene Expr Patterns. 2006;6:1000-6 pubmed
    ..This was in contrast to Slc12a1 (NKCC2), where expression was excluded from the glomerulus. Extra-renal expression of Slc12a2 was examined in 13...
  29. Zaarour N, Defontaine N, Demaretz S, Azroyan A, Cheval L, Laghmani K. Secretory carrier membrane protein 2 regulates exocytic insertion of NKCC2 into the cell membrane. J Biol Chem. 2011;286:9489-502 pubmed publisher
    The renal-specific Na-K-2Cl co-transporter, NKCC2, plays a pivotal role in regulating body salt levels and blood pressure. NKCC2 mutations lead to type I Bartter syndrome, a life-threatening kidney disease...
  30. Takahashi N, Chernavvsky D, Gomez R, Igarashi P, Gitelman H, Smithies O. Uncompensated polyuria in a mouse model of Bartter's syndrome. Proc Natl Acad Sci U S A. 2000;97:5434-9 pubmed
    We have used homologous recombination to disrupt the mouse gene coding for the NaK2Cl cotransporter (NKCC2) expressed in kidney epithelial cells of the thick ascending limb and macula densa...
  31. Mutig K, Kahl T, Saritas T, Godes M, Persson P, Bates J, et al. Activation of the bumetanide-sensitive Na+,K+,2Cl- cotransporter (NKCC2) is facilitated by Tamm-Horsfall protein in a chloride-sensitive manner. J Biol Chem. 2011;286:30200-10 pubmed publisher
    ..transport of NaCl across thick ascending limb (TAL) epithelium is accomplished by Na(+),K(+),2Cl(-) cotransporter (NKCC2)...
  32. Ji T, Liu S, Zheng L, Wang Q, Dou Z, Zhang Y, et al. Cellular distribution of NKCC2 in the gastric mucosa and its response to short-term osmotic shock. Cell Tissue Res. 2012;348:155-65 pubmed publisher
    The Na(+)-K(+)-2Cl(-) cotransporter-2 (NKCC2) has long been recognized as a "kidney-specific" transporter and is important in salt reabsorption...
  33. Seaayfan E, Defontaine N, Demaretz S, Zaarour N, Laghmani K. OS9 Protein Interacts with Na-K-2Cl Co-transporter (NKCC2) and Targets Its Immature Form for the Endoplasmic Reticulum-associated Degradation Pathway. J Biol Chem. 2016;291:4487-502 pubmed publisher
    Mutations in the renal specific Na-K-2Cl co-transporter (NKCC2) lead to type I Bartter syndrome, a life-threatening kidney disease featuring arterial hypotension along with electrolyte abnormalities...
  34. Rinehart J, Kahle K, de los Heros P, Vazquez N, Meade P, Wilson F, et al. WNK3 kinase is a positive regulator of NKCC2 and NCC, renal cation-Cl- cotransporters required for normal blood pressure homeostasis. Proc Natl Acad Sci U S A. 2005;102:16777-82 pubmed
    ..SLC12A family, we used coexpression studies in Xenopus oocytes to investigate the effect of WNK3 on NCC and NKCC2, related kidney-specific transporters that mediate apical NaCl reabsorption in the thick ascending limb and distal ..
  35. Plata C, Meade P, Vazquez N, Hebert S, Gamba G. Functional properties of the apical Na+-K+-2Cl- cotransporter isoforms. J Biol Chem. 2002;277:11004-12 pubmed
    ..When expressed in Xenopus oocytes the mBSC1-A isoform showed higher capacity of transport, with no difference in the amount of surface expression...
  36. Igarashi P, Vanden Heuvel G, Payne J, Forbush B. Cloning, embryonic expression, and alternative splicing of a murine kidney-specific Na-K-Cl cotransporter. Am J Physiol. 1995;269:F405-18 pubmed
    A full-length cDNA encoding the murine renal Na-K-Cl cotransporter (NKCC2) was cloned using library screening and anchored polymerase chain reaction. The deduced protein sequence contained 1,095 amino acids and was 93...
  37. Kim Y, Kim W, Nam S, Choi A, Kim H, Kim Y, et al. Role of Prox1 in the Transforming Ascending Thin Limb of Henle's Loop during Mouse Kidney Development. PLoS ONE. 2015;10:e0127429 pubmed publisher
    ..Our data show that Prox1 is expressed in the transdifferentiating region from the NKCC2-positive thick ascending limb, into the CLC-K1-positive ascending thin limb of Henle's loop beginning at embryonic ..
  38. Mount D, Baekgaard A, Hall A, Plata C, Xu J, Beier D, et al. Isoforms of the Na-K-2Cl cotransporter in murine TAL I. Molecular characterization and intrarenal localization. Am J Physiol. 1999;276:F347-58 pubmed
    We have identified several alternatively spliced cDNAs encoding mBSC1, an apical bumetanide-sensitive Na+-K+-2Cl- cotransporter from mouse kidney...
  39. Battula S, Hao S, Pedraza P, Stier C, Ferreri N. Tumor necrosis factor-alpha is an endogenous inhibitor of Na+-K+-2Cl- cotransporter (NKCC2) isoform A in the thick ascending limb. Am J Physiol Renal Physiol. 2011;301:F94-100 pubmed publisher
    The effects of TNF gene deletion on renal Na(+)-K(+)-2Cl(-) cotransporter (NKCC2) expression and activity were determined...
  40. Wang J, Pravenec M, Kren V, Kurtz T. Linkage mapping of the Na-K-2Cl cotransporter gene (Slc12a1) to rat chromosome 3. Mamm Genome. 1997;8:379 pubmed
  41. Horsch M, Beckers J, Fuchs H, Gailus Durner V, HrabÄ› de Angelis M, Rathkolb B, et al. Uromodulin retention in thick ascending limb of Henle's loop affects SCD1 in neighboring proximal tubule: renal transcriptome studies in mouse models of uromodulin-associated kidney disease. PLoS ONE. 2014;9:e113125 pubmed publisher
    ..This finding demonstrates that a cross talk between two functionally distinct tubular segments of the kidney, the TALH segment and the S3 segment of proximal tubule, exists. ..
  42. Qian C, Knol J, Igarashi P, Lin F, Zylstra U, Teh B, et al. Cystic renal neoplasia following conditional inactivation of apc in mouse renal tubular epithelium. J Biol Chem. 2005;280:3938-45 pubmed
    ..Our results confirm an important role for proper regulation of Wnt/beta-catenin signaling in renal development and provide evidence that dysregulation of the pathway can initiate tumorigenesis in the kidney. ..
  43. Chung E, Deacon P, Marable S, Shin J, Park J. Notch signaling promotes nephrogenesis by downregulating Six2. Development. 2016;143:3907-3913 pubmed
    ..Our results demonstrate how cell fates of progenitors are regulated by a transcription factor governing progenitor status and by a differentiation signal in nephrogenesis. ..
  44. Igarashi P, Whyte D, Li K, Nagami G. Cloning and kidney cell-specific activity of the promoter of the murine renal Na-K-C1 cotransporter gene. J Biol Chem. 1996;271:9666-74 pubmed
    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...
  45. Hao S, Zhao H, Darzynkiewicz Z, Battula S, Ferreri N. Differential regulation of NFAT5 by NKCC2 isoforms in medullary thick ascending limb (mTAL) cells. Am J Physiol Renal Physiol. 2011;300:F966-75 pubmed publisher
    The effects of Na(+)-K(+)-2Cl(-) cotransporter type 2 (NKCC2) isoforms on the regulation of nuclear factor of activated T cells isoform 5 (NFAT5) were determined in mouse medullary thick ascending limb (mTAL) cells exposed to high NaCl ..
  46. Werth M, Walentin K, Aue A, Schönheit J, Wuebken A, Pode Shakked N, et al. The transcription factor grainyhead-like 2 regulates the molecular composition of the epithelial apical junctional complex. Development. 2010;137:3835-45 pubmed publisher
    ..Together, our data provide evidence that Grhl2 acts as a target gene-associated transcriptional activator of apical junctional complex components and, thereby, crucially participates in epithelial differentiation. ..
  47. Mugford J, Sipila P, Kobayashi A, Behringer R, McMahon A. Hoxd11 specifies a program of metanephric kidney development within the intermediate mesoderm of the mouse embryo. Dev Biol. 2008;319:396-405 pubmed publisher
    ..This program maintains tubule forming progenitors and instructs a metanephric specific pattern of nephron differentiation. ..
  48. Massa F, Garbay S, Bouvier R, Sugitani Y, Noda T, Gubler M, et al. Hepatocyte nuclear factor 1? controls nephron tubular development. Development. 2013;140:886-96 pubmed publisher
    ..In addition, these studies define a novel structural and functional component of S-shaped bodies at the origin of tubule formation. ..
  49. Lee H, Kim W, Song H, Yang C, Han K, Kwon H, et al. Sequential expression of NKCC2, TonEBP, aldose reductase, and urea transporter-A in developing mouse kidney. Am J Physiol Renal Physiol. 2007;292:F269-77 pubmed
    This study was conducted to test the hypothesis that, during renal development, the Na-K-2Cl cotransporter type 2 (NKCC2) activates the tonicity-responsive enhancer binding protein (TonEBP) transcription factor by creating medullary ..
  50. Schiessl I, Rosenauer A, Kattler V, Minuth W, Oppermann M, Castrop H. Dietary salt intake modulates differential splicing of the Na-K-2Cl cotransporter NKCC2. Am J Physiol Renal Physiol. 2013;305:F1139-48 pubmed publisher
    ..loop of Henle (TAL) and macula densa salt sensing crucially depend on the function of the Na/K/2Cl cotransporter NKCC2. The NKCC2 gene gives rise to at least three different full-length NKCC2 isoforms derived from differential ..
  51. Self M, Lagutin O, Bowling B, Hendrix J, Cai Y, Dressler G, et al. Six2 is required for suppression of nephrogenesis and progenitor renewal in the developing kidney. EMBO J. 2006;25:5214-28 pubmed
    ..We propose that in the developing kidney, Six2 activity is required for maintaining the mesenchymal progenitor population in an undifferentiated state by opposing the inductive signals emanating from the ureteric bud...
  52. Yamaguchi Y, Yonemura S, Takada S. Grainyhead-related transcription factor is required for duct maturation in the salivary gland and the kidney of the mouse. Development. 2006;133:4737-48 pubmed
    ..Furthermore, the composition of saliva and urine was abnormal in these mice. These results indicate that Cp2l1 expression is required for normal duct development in both the salivary gland and kidney. ..
  53. Gimenez I, Forbush B. The residues determining differences in ion affinities among the alternative splice variants F, A, and B of the mammalian renal Na-K-Cl cotransporter (NKCC2). J Biol Chem. 2007;282:6540-7 pubmed
    Three alternatively spliced variants of the renal Na-K-Cl cotransporter (NKCC2) are found in distinct regions of the thick ascending limb of the mammalian kidney; these variants mediate Na(+)K(+)2Cl(-) transport with different ion ..
  54. Zaarour N, Demaretz S, Defontaine N, Mordasini D, Laghmani K. A highly conserved motif at the COOH terminus dictates endoplasmic reticulum exit and cell surface expression of NKCC2. J Biol Chem. 2009;284:21752-64 pubmed publisher
    Mutations in the apically located Na(+)-K(+)-2Cl(-) co-transporter, NKCC2, lead to type I Bartter syndrome, a life-threatening kidney disorder, yet the mechanisms underlying the regulation of mutated NKCC2 proteins in renal cells have ..
  55. Sonalker P, Jackson E. Norepinephrine, via beta-adrenoceptors, regulates bumetanide-sensitive cotransporter type 1 expression in thick ascending limb cells. Hypertension. 2007;49:1351-7 pubmed
  56. Gamba G, Miyanoshita A, Lombardi M, Lytton J, Lee W, Hediger M, et al. Molecular cloning, primary structure, and characterization of two members of the mammalian electroneutral sodium-(potassium)-chloride cotransporter family expressed in kidney. J Biol Chem. 1994;269:17713-22 pubmed
    ..These proteins establish a new family of Na(+)-(K+)-Cl- cotransporters. ..
  57. Takahashi N, Brooks H, Wade J, Liu W, Kondo Y, Ito S, et al. Posttranscriptional compensation for heterozygous disruption of the kidney-specific NaK2Cl cotransporter gene. J Am Soc Nephrol. 2002;13:604-10 pubmed
    Mice homozygous for a loss of function mutation of the kidney-specific NaK2Cl cotransporter, BSC1/NKCC2, do not survive. Here the effects of loss of one copy of the gene are studied...
  58. Piechotta K, Lu J, Delpire E. Cation chloride cotransporters interact with the stress-related kinases Ste20-related proline-alanine-rich kinase (SPAK) and oxidative stress response 1 (OSR1). J Biol Chem. 2002;277:50812-9 pubmed
    ..proline-alanine-rich kinase (SPAK) and oxidative stress response 1 (OSR1) with the cotransporters KCC3, NKCC1, and NKCC2 but not KCC1 and KCC4...
  59. McCormick J, Mutig K, Nelson J, Saritas T, Hoorn E, Yang C, et al. A SPAK isoform switch modulates renal salt transport and blood pressure. Cell Metab. 2011;14:352-64 pubmed publisher
    ..An emerging model suggests that bumetanide- and thiazide-sensitive NaCl transporters (NKCC2 and NCC) along these segments are phosphorylated and activated by WNK kinases, via SPAK and OSR1...
  60. Gu B, Sun P, Yuan Y, Moraes R, Li A, Teng A, et al. Pygo2 expands mammary progenitor cells by facilitating histone H3 K4 methylation. J Cell Biol. 2009;185:811-26 pubmed publisher
  61. Blaesse P, Airaksinen M, Rivera C, Kaila K. Cation-chloride cotransporters and neuronal function. Neuron. 2009;61:820-38 pubmed publisher
    ..The rapidly expanding work on CCCs promotes our understanding of fundamental mechanisms that control brain development and functions under normal and pathophysiological conditions. ..
  62. Kemter E, Rathkolb B, Becker L, Bolle I, Busch D, Dalke C, et al. Standardized, systemic phenotypic analysis of Slc12a1I299F mutant mice. J Biomed Sci. 2014;21:68 pubmed publisher
    Type I Bartter syndrome is a recessive human nephropathy caused by loss-of-function mutations in the SLC12A1 gene coding for the Na+-K+-2Cl- cotransporter NKCC2...
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