Slc12a1

Summary

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

Top Publications

  1. pmc Regulation of the renal-specific Na+-K+-2Cl- co-transporter NKCC2 by AMP-activated protein kinase (AMPK)
    Scott A Fraser
    The Burnet Research Institute, Austin Health, Studley Road, Heidelberg, Victoria 3084, Australia
    Biochem J 405:85-93. 2007
  2. doi Mutation of the Na(+)-K(+)-2Cl(-) cotransporter NKCC2 in mice is associated with severe polyuria and a urea-selective concentrating defect without hyperreninemia
    Elisabeth Kemter
    Molecular Animal Breeding and Biotechnology, and Laboratory for Functional Genome Analysis LAFUGA, Gene Center, LMU Munich, Munich, Germany
    Am J Physiol Renal Physiol 298:F1405-15. 2010
  3. pmc OS9 Protein Interacts with Na-K-2Cl Co-transporter (NKCC2) and Targets Its Immature Form for the Endoplasmic Reticulum-associated Degradation Pathway
    Elie Seaayfan
    From INSERM, Centre de Recherche des Cordeliers, U1138, Paris 75006, France, CNRS, ERL8228, Paris 75006, France, Universite Pierre et Marie Curie, Paris 75006, France, and Universite Paris Descartes, Paris 75005, France
    J Biol Chem 291:4487-502. 2016
  4. doi Secreted Wnt antagonist Dickkopf-1 controls kidney papilla development coordinated by Wnt-7b signalling
    Ilkka Pietilä
    Oulu Center for Cell Matrix Research, Biocenter Oulu, Laboratory of Developmental Biology and Department of Medical Biochemistry and Molecular Biology, Institute of Biomedicine, University of Oulu, Finland
    Dev Biol 353:50-60. 2011
  5. ncbi Cation chloride cotransporters interact with the stress-related kinases Ste20-related proline-alanine-rich kinase (SPAK) and oxidative stress response 1 (OSR1)
    Kerstin Piechotta
    Department of Anesthesiology and Center for Molecular Neuroscience, Vanderbilt University, Medical Center, Nashville, Tennessee 37232, USA
    J Biol Chem 277:50812-9. 2002
  6. ncbi Functional properties of the apical Na+-K+-2Cl- cotransporter isoforms
    Consuelo Plata
    Molecular Physiology Unit, Instituto de Investigaciones Biomedicas, Universidad Nacional Autónoma de México and Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Tlalpan 14000, Mexico City, Mexico
    J Biol Chem 277:11004-12. 2002
  7. doi Genetic dissection of sodium and potassium transport along the aldosterone-sensitive distal nephron: importance in the control of blood pressure and hypertension
    Bernard C Rossier
    University of Lausanne, Lausanne, Switzerland
    FEBS Lett 587:1929-41. 2013
  8. doi Dietary salt intake modulates differential splicing of the Na-K-2Cl cotransporter NKCC2
    Ina Maria Schiessl
    Institute of Physiology, Univ of Regensburg, Universitätsstr 31, 93040 Regensburg, Germany
    Am J Physiol Renal Physiol 305:F1139-48. 2013
  9. doi Novel mechanisms of Na+ retention in obesity: phosphorylation of NKCC2 and regulation of SPAK/OSR1 by AMPK
    Matthew Davies
    Kidney Laboratory, Institute for Breathing and Sleep, University of Melbourne, Heidelberg, Victoria, Australia Department of Nephrology, University of Melbourne, Heidelberg, Victoria, Australia Department of Medicine, University of Melbourne, Heidelberg, Victoria, Australia and
    Am J Physiol Renal Physiol 307:F96-F106. 2014
  10. pmc 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
    Marion Horsch
    German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München GmbH, German Research Center for Environmental Health, Neuherberg, Germany
    PLoS ONE 9:e113125. 2014

Research Grants

  1. Cux-1 and cell cycle regulation in kidney development
    Gregory Vanden Heuvel; Fiscal Year: 2009

Scientific Experts

  • H Castrop
  • Nobuyuki Takahashi
  • Bernard C Rossier
  • James A McCormick
  • Gregory Vanden Heuvel
  • Ignacio Gimenez
  • Bernhard Aigner
  • Scott A Fraser
  • Elisabeth Kemter
  • Ciaran Richardson
  • D B Mount
  • Nancy Zaarour
  • Shoujin Hao
  • Kamel Laghmani
  • Nadia Defontaine
  • Sylvie Demaretz
  • Mona Oppermann
  • Gerardo Gamba
  • Nicholas R Ferreri
  • Sailaja Battula
  • Kerim Mutig
  • Jin Kim
  • Wan Young Kim
  • Sebastian Bachmann
  • Jiandong Zhang
  • Elie Seaayfan
  • Yu Mi Kim
  • Saeed Alshahrani
  • Yue Zhang
  • Matthew Davies
  • Marion Horsch
  • Filippo Massa
  • Jingjing Wu
  • Ina Maria Schiessl
  • A Paliege
  • T Ji
  • Shih Hua Lin
  • Vidya K Nagalakshmi
  • Shinichi Uchida
  • Zhen Liu
  • Ilkka Pietilä
  • Michael Bader
  • Max Werth
  • Uyen Tran
  • Juliane Reiche
  • Andrew P McMahon
  • Lydie Cheval
  • Peter Blaesse
  • Hyun Woo Jeong
  • Bingnan Gu
  • Joshua W Mugford
  • Franziska Theilig
  • Hyun Wook Lee
  • Boubacar Benziane
  • Prajakta A Sonalker
  • Melina Narlis
  • Diane Mizel
  • Cuiling Li
  • Jurgen Schnermann
  • Josie Briggs
  • Chuxia Deng
  • Michelle Self
  • Yoshifumi Yamaguchi
  • Celine Delaloy
  • Jesse Rinehart
  • Chao Nan Qian
  • Norma Vazquez
  • Steven C Hebert
  • P Igarashi
  • Patricia Meade
  • Matthew A Sparks
  • Alexander D Jeffs
  • Steven D Crowley
  • Alicia A McDonough
  • Nathan P Rudemiller
  • Robert Griffiths
  • Mehul B Patel
  • Norah S Karlovich
  • Min Wu
  • A Rum Choi
  • Songming Huang
  • Ying Sun
  • Mohammed Mashari Almutairi
  • Mohamed Mahmoud Almiahuob
  • Mauricio Di Fulvio
  • Hyang Kim
  • Hak Soo Kim
  • Shams Kursan
  • Guixia Ding
  • Zhanjun Jia

Detail Information

Publications67

  1. pmc Regulation of the renal-specific Na+-K+-2Cl- co-transporter NKCC2 by AMP-activated protein kinase (AMPK)
    Scott A Fraser
    The Burnet Research Institute, Austin Health, Studley Road, Heidelberg, Victoria 3084, Australia
    Biochem J 405:85-93. 2007
    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. doi Mutation of the Na(+)-K(+)-2Cl(-) cotransporter NKCC2 in mice is associated with severe polyuria and a urea-selective concentrating defect without hyperreninemia
    Elisabeth Kemter
    Molecular Animal Breeding and Biotechnology, and Laboratory for Functional Genome Analysis LAFUGA, Gene Center, LMU Munich, Munich, Germany
    Am J Physiol Renal Physiol 298:F1405-15. 2010
    ..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. pmc OS9 Protein Interacts with Na-K-2Cl Co-transporter (NKCC2) and Targets Its Immature Form for the Endoplasmic Reticulum-associated Degradation Pathway
    Elie Seaayfan
    From INSERM, Centre de Recherche des Cordeliers, U1138, Paris 75006, France, CNRS, ERL8228, Paris 75006, France, Universite Pierre et Marie Curie, Paris 75006, France, and Universite Paris Descartes, Paris 75005, France
    J Biol Chem 291:4487-502. 2016
    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...
  4. doi Secreted Wnt antagonist Dickkopf-1 controls kidney papilla development coordinated by Wnt-7b signalling
    Ilkka Pietilä
    Oulu Center for Cell Matrix Research, Biocenter Oulu, Laboratory of Developmental Biology and Department of Medical Biochemistry and Molecular Biology, Institute of Biomedicine, University of Oulu, Finland
    Dev Biol 353:50-60. 2011
    ..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. ncbi Cation chloride cotransporters interact with the stress-related kinases Ste20-related proline-alanine-rich kinase (SPAK) and oxidative stress response 1 (OSR1)
    Kerstin Piechotta
    Department of Anesthesiology and Center for Molecular Neuroscience, Vanderbilt University, Medical Center, Nashville, Tennessee 37232, USA
    J Biol Chem 277:50812-9. 2002
    ..proline-alanine-rich kinase (SPAK) and oxidative stress response 1 (OSR1) with the cotransporters KCC3, NKCC1, and NKCC2 but not KCC1 and KCC4...
  6. ncbi Functional properties of the apical Na+-K+-2Cl- cotransporter isoforms
    Consuelo Plata
    Molecular Physiology Unit, Instituto de Investigaciones Biomedicas, Universidad Nacional Autónoma de México and Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Tlalpan 14000, Mexico City, Mexico
    J Biol Chem 277:11004-12. 2002
    ..When expressed in Xenopus oocytes the mBSC1-A isoform showed higher capacity of transport, with no difference in the amount of surface expression...
  7. doi Genetic dissection of sodium and potassium transport along the aldosterone-sensitive distal nephron: importance in the control of blood pressure and hypertension
    Bernard C Rossier
    University of Lausanne, Lausanne, Switzerland
    FEBS Lett 587:1929-41. 2013
    ..This will allow to design rational strategies for the treatment of hypertension and for the development of the next generation of diuretics...
  8. doi Dietary salt intake modulates differential splicing of the Na-K-2Cl cotransporter NKCC2
    Ina Maria Schiessl
    Institute of Physiology, Univ of Regensburg, Universitätsstr 31, 93040 Regensburg, Germany
    Am J Physiol Renal Physiol 305:F1139-48. 2013
    ..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 ..
  9. doi Novel mechanisms of Na+ retention in obesity: phosphorylation of NKCC2 and regulation of SPAK/OSR1 by AMPK
    Matthew Davies
    Kidney Laboratory, Institute for Breathing and Sleep, University of Melbourne, Heidelberg, Victoria, Australia Department of Nephrology, University of Melbourne, Heidelberg, Victoria, Australia Department of Medicine, University of Melbourne, Heidelberg, Victoria, Australia and
    Am J Physiol Renal Physiol 307:F96-F106. 2014
    ..When we examined Na(+) transporter expression, Na(+)-K(+)-2Cl(-) cotransporter (NKCC2) was unchanged in whole kidney and reduced in the cortex, Na(+)-Cl(-) cotransporter (NCC) and α-epithelial Na(+) ..
  10. pmc 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
    Marion Horsch
    German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München GmbH, German Research Center for Environmental Health, Neuherberg, Germany
    PLoS ONE 9:e113125. 2014
    ..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. ..
  11. pmc Role of Prox1 in the Transforming Ascending Thin Limb of Henle's Loop during Mouse Kidney Development
    Yu Mi Kim
    Department of Anatomy and Cell Death Disease Research Center, College of Medicine, The Catholic University of Korea, Seoul, Korea
    PLoS ONE 10:e0127429. 2015
    ..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 ..
  12. pmc Inhibition of Mitochondrial Complex-1 Prevents the Downregulation of NKCC2 and ENaCα in Obstructive Kidney Disease
    Yue Zhang
    1 Department of Nephrology, Nanjing Children s Hospital, Affiliated with Nanjing Medical University, Nanjing 210008, China 2 Institute of Pediatrics, Nanjing Medical University, Nanjing, China 3 Nanjing Key Laboratory of Pediatrics, Nanjing Children Hospital, Affiliated with Nanjing Medical University, Nanjing 210008, China
    Sci Rep 5:12480. 2015
    ..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...
  13. pmc Increased Slc12a1 expression in β-cells and improved glucose disposal in Slc12a2 heterozygous mice
    Saeed Alshahrani
    Department of Pharmacology and ToxicologyBoonshoft School of Medicine, Wright State University, 3640 Colonel Glenn Highway, 216 HSB, Dayton, Ohio 45435, USAPacific Northwest Diabetes Research InstituteSeattle, Washington 98122, USA
    J Endocrinol 227:153-65. 2015
    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...
  14. pmc Interleukin-1 Receptor Activation Potentiates Salt Reabsorption in Angiotensin II-Induced Hypertension via the NKCC2 Co-transporter in the Nephron
    Jiandong Zhang
    Division of Nephrology, Department of Medicine, Duke University and Durham VA Medical Centers, Durham, NC 27710, USA
    Cell Metab 23:360-8. 2016
    ..deficiency or blockade limits blood pressure elevation in this model by mitigating sodium reabsorption via the NKCC2 co-transporter in the nephron...
  15. doi Hepatocyte nuclear factor 1β controls nephron tubular development
    Filippo Massa
    Expression Génique, Développement et Maladies EGDM Team, Inserm U1016, CNRS UMR 8104, Université Paris Descartes Institut Cochin Département deGénétique et Développement, 75014 Paris, France
    Development 140:886-96. 2013
    ..In addition, these studies define a novel structural and functional component of S-shaped bodies at the origin of tubule formation...
  16. pmc Multiple evolutionarily conserved Di-leucine like motifs in the carboxyl terminus control the anterograde trafficking of NKCC2
    Nancy Zaarour
    INSERM, Centre de Recherche des Cordeliers, UMRS872, Paris, France
    J Biol Chem 287:42642-53. 2012
    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...
  17. doi Synergistical effect of 20-HETE and high salt on NKCC2 protein and blood pressure via ubiquitin-proteasome pathway
    Jingjing Wu
    Department of Clinical Genetics, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China
    Hum Genet 132:179-87. 2013
    ..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...
  18. pmc Dicer regulates the development of nephrogenic and ureteric compartments in the mammalian kidney
    Vidya K Nagalakshmi
    Department of Cell Biology, University of Virginia School of Medicine, Charlottesville, Virginia 22908, USA
    Kidney Int 79:317-30. 2011
    ..Furthermore, an understanding of miRNA action may provide new insights into the etiology and pathogenesis of renal cyst-based kidney disease...
  19. doi Group VIA phospholipase A2 is a target for vasopressin signaling in the thick ascending limb
    A Paliege
    Dept of Anatomy, Charite Universitatsmedizin Berlin, Philippstrasse 12, Berlin, Germany
    Am J Physiol Renal Physiol 302:F865-74. 2012
    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. ncbi Expression of the basolateral Na-K-Cl cotransporter during mouse nephrogenesis and embryonic development
    Gregory B Vanden Heuvel
    Department of Anatomy and Cell Biology, University of Kansas Medical Center, Kansas City, KS 66160, USA
    Gene Expr Patterns 6:1000-6. 2006
    ..This was in contrast to Slc12a1 (NKCC2), where expression was excluded from the glomerulus. Extra-renal expression of Slc12a2 was examined in 13...
  21. pmc Regulation of the NKCC2 ion cotransporter by SPAK-OSR1-dependent and -independent pathways
    Ciaran Richardson
    MRC Protein Phosphorylation Unit, College of Life Sciences, University of Dundee, Dow Street, Dundee DD1 5EH, UK
    J Cell Sci 124:789-800. 2011
    ..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 ..
  22. doi Cellular distribution of NKCC2 in the gastric mucosa and its response to short-term osmotic shock
    T Ji
    Department of Physiology, School of Basic Medical Sciences, Capital Medical University, Beijing, China
    Cell Tissue Res 348:155-65. 2012
    The Na(+)-K(+)-2Cl(-) cotransporter-2 (NKCC2) has long been recognized as a "kidney-specific" transporter and is important in salt reabsorption...
  23. pmc NKCC2A and NFAT5 regulate renal TNF production induced by hypertonic NaCl intake
    Shoujin Hao
    Dept of Pharmacology, New York Medical College, Valhalla, NY 10595, USA
    Am J Physiol Renal Physiol 304:F533-42. 2013
    ..hypertonic NaCl intake increases renal TNF production by a pathway involving the Na(+)-K(+)-2Cl(-) cotransporter (NKCC2). A 2...
  24. pmc Activation of the bumetanide-sensitive Na+,K+,2Cl- cotransporter (NKCC2) is facilitated by Tamm-Horsfall protein in a chloride-sensitive manner
    Kerim Mutig
    Department of Anatomy, Charite Universitatsmedizin Berlin, Berlin, Germany
    J Biol Chem 286:30200-10. 2011
    ..transport of NaCl across thick ascending limb (TAL) epithelium is accomplished by Na(+),K(+),2Cl(-) cotransporter (NKCC2)...
  25. pmc Tumor necrosis factor-alpha is an endogenous inhibitor of Na+-K+-2Cl- cotransporter (NKCC2) isoform A in the thick ascending limb
    Sailaja Battula
    Dept of Pharmacology, New York Medical College, Valhalla, NY 10595, USA
    Am J Physiol Renal Physiol 301:F94-100. 2011
    The effects of TNF gene deletion on renal Na(+)-K(+)-2Cl(-) cotransporter (NKCC2) expression and activity were determined...
  26. pmc A SPAK isoform switch modulates renal salt transport and blood pressure
    James A McCormick
    Division of Nephrology and Hypertension, Oregon Health and Science University, Portland, OR 97239 3098, USA
    Cell Metab 14:352-64. 2011
    ..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...
  27. pmc Impaired phosphorylation of Na(+)-K(+)-2Cl(-) cotransporter by oxidative stress-responsive kinase-1 deficiency manifests hypotension and Bartter-like syndrome
    Shih Hua Lin
    Division of Nephrology, Department of Medicine, Tri Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan
    Proc Natl Acad Sci U S A 108:17538-43. 2011
    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...
  28. pmc Differential regulation of NFAT5 by NKCC2 isoforms in medullary thick ascending limb (mTAL) cells
    Shoujin Hao
    Department of Pharmacology, New York Medical College, Valhalla, New York, USA
    Am J Physiol Renal Physiol 300:F966-75. 2011
    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 ..
  29. pmc Secretory carrier membrane protein 2 regulates exocytic insertion of NKCC2 into the cell membrane
    Nancy Zaarour
    INSERM, Centre de Recherche des Cordeliers, UMRS 872, CNRS, ERL7226, 75006 Paris, France
    J Biol Chem 286:9489-502. 2011
    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. pmc Downregulation of NCC and NKCC2 cotransporters by kidney-specific WNK1 revealed by gene disruption and transgenic mouse models
    Zhen Liu
    Division of Nephrology, Department of Medicine, UT Southwestern Medical Center, Dallas, TX 75390 8856, USA
    Hum Mol Genet 20:855-66. 2011
    ..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...
  31. doi The transcription factor grainyhead-like 2 regulates the molecular composition of the epithelial apical junctional complex
    Max Werth
    Max Delbruck Center for Molecular Medicine, Robert Rossle Strasse 10, 13125 Berlin, Germany
    Development 137:3835-45. 2010
    ..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...
  32. doi Cation-chloride cotransporters and neuronal function
    Peter Blaesse
    Department of Biological and Environmental Sciences, University of Helsinki, Viikinkaari 1, FIN 00014, Helsinki, Finland
    Neuron 61:820-38. 2009
    ..The rapidly expanding work on CCCs promotes our understanding of fundamental mechanisms that control brain development and functions under normal and pathophysiological conditions...
  33. pmc SORLA/SORL1 functionally interacts with SPAK to control renal activation of Na(+)-K(+)-Cl(-) cotransporter 2
    Juliane Reiche
    Max Delbruck Center for Molecular Medicine, Charite, Universitatsmedizin, 13125 Berlin, Germany
    Mol Cell Biol 30:3027-37. 2010
    ..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...
  34. pmc The RNA-binding protein bicaudal C regulates polycystin 2 in the kidney by antagonizing miR-17 activity
    Uyen Tran
    Department of Cell Biology and Anatomy, LSU Health Sciences Center, MEB 6A12, 1901 Perdido Street, New Orleans, LA 70112, USA
    Development 137:1107-16. 2010
    ..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...
  35. pmc Inactivation of Notch signaling in the renal collecting duct causes nephrogenic diabetes insipidus in mice
    Hyun Woo Jeong
    Department of Biological Sciences, Seoul National University, Seoul, Republic of Korea
    J Clin Invest 119:3290-300. 2009
    ..Our data demonstrate that Notch signaling is required for the development of the mammalian renal collecting duct and principal cell differentiation and indicate that pathway dysregulation may contribute to distal renal tubular disorders...
  36. ncbi 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
    Mona Oppermann
    National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892 1370, USA
    J Am Soc Nephrol 17:2143-52. 2006
    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...
  37. ncbi Molecular cloning, primary structure, and characterization of two members of the mammalian electroneutral sodium-(potassium)-chloride cotransporter family expressed in kidney
    G Gamba
    Harvard Center for Study of Kidney Disease, Harvard Medical School, Boston, Massachusetts
    J Biol Chem 269:17713-22. 1994
    ..These proteins establish a new family of Na(+)-(K+)-Cl- cotransporters...
  38. ncbi Localization of the renal Na-K-Cl cotransporter gene (Slc12a1) on mouse chromosome 2
    S E Quaggin
    Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06520 8029, USA
    Mamm Genome 6:557-8. 1995
  39. ncbi Mouse chromosomal location of three epithelial sodium channel subunit genes and an apical sodium chloride cotransporter gene
    B G Pathak
    Mammalian Genetics Laboratory, ABL Basic Research Program, NCI Frederick Cancer Research and Development Center, Frederick, Maryland, 21702, USA
    Genomics 33:124-7. 1996
    ..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...
  40. ncbi Cloning and kidney cell-specific activity of the promoter of the murine renal Na-K-C1 cotransporter gene
    P Igarashi
    Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06520
    J Biol Chem 271:9666-74. 1996
    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...
  41. ncbi Bartter's syndrome, hypokalaemic alkalosis with hypercalciuria, is caused by mutations in the Na-K-2Cl cotransporter NKCC2
    D B Simon
    Howard Hughes Medical Institute, Department of Medicine, Boyer Center for Molecular Medicine, Yale University School of Medicine, New Haven, Connecticut 06510, USA
    Nat Genet 13:183-8. 1996
    ..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...
  42. ncbi Molecular cloning and functional expression of the K-Cl cotransporter from rabbit, rat, and human. A new member of the cation-chloride cotransporter family
    C M Gillen
    Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, Connecticut 06520, USA
    J Biol Chem 271:16237-44. 1996
    ..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...
  43. ncbi Linkage mapping of the Na-K-2Cl cotransporter gene (Slc12a1) to rat chromosome 3
    J Wang
    Department of Laboratory Medicine, University of California, San Francisco, California 94143, USA
    Mamm Genome 8:379. 1997
  44. ncbi Isoforms of the Na-K-2Cl cotransporter in murine TAL I. Molecular characterization and intrarenal localization
    D B Mount
    Division of Nephrology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA
    Am J Physiol 276:F347-58. 1999
    We have identified several alternatively spliced cDNAs encoding mBSC1, an apical bumetanide-sensitive Na+-K+-2Cl- cotransporter from mouse kidney...
  45. ncbi Isoforms of the Na-K-2Cl cotransporter in murine TAL II. Functional characterization and activation by cAMP
    C Plata
    Molecular Physiology Unit, Department of Nephrology and Mineral Metabolism, Instituto Nacional de la Nutrición Salvador Zubirán and Department of Medicine, Instituto de Investigaciones Biomedicas, National University of Mexico, Mexico City, Mexico
    Am J Physiol 276:F359-66. 1999
    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...
  46. pmc Uncompensated polyuria in a mouse model of Bartter's syndrome
    N Takahashi
    Department of Pathology and Laboratory Medicine and Division of Nephrology, University of North Carolina, Chapel Hill, NC 27599, USA
    Proc Natl Acad Sci U S A 97:5434-9. 2000
    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...
  47. ncbi Intrarenal and cellular localization of CLC-K2 protein in the mouse kidney
    K Kobayashi
    Department of Pediatrics, Tokyo Medical and Dental University, School of Medicine, 1 5 45 Yushima, Bunkyo ku, Tokyo, 113, Japan
    J Am Soc Nephrol 12:1327-34. 2001
    ..These aspects of CLC-K2 localization suggest that CLC-K2 is important in Cl(-) transport in the distal nephron segments...
  48. ncbi Posttranscriptional compensation for heterozygous disruption of the kidney-specific NaK2Cl cotransporter gene
    Nobuyuki Takahashi
    Department of Pathology and Laboratory Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599 7525, USA
    J Am Soc Nephrol 13:604-10. 2002
    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...
  49. ncbi Cystic renal neoplasia following conditional inactivation of apc in mouse renal tubular epithelium
    Chao Nan Qian
    Laboratories of Cancer Genetics and Cell Signaling and Carcinogenesis, Van Andel Research Institute, Grand Rapids, Michigan 49508, USA
    J Biol Chem 280:3938-45. 2005
    ..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...
  50. ncbi Ren1c homozygous null mice are hypotensive and polyuric, but heterozygotes are indistinguishable from wild-type
    Nobuyuki Takahashi
    Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, 701 Brinkhous Bullitt Building, Chapel Hill, NC 27599 7525, USA
    J Am Soc Nephrol 16:125-32. 2005
    ..These results demonstrate that renin is the only enzyme capable of maintaining plasma angiotensins and that renin expression in the kidney is very tightly regulated at the mRNA level...
  51. pmc WNK3 kinase is a positive regulator of NKCC2 and NCC, renal cation-Cl- cotransporters required for normal blood pressure homeostasis
    Jesse Rinehart
    Department of Genetics, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06510, USA
    Proc Natl Acad Sci U S A 102:16777-82. 2005
    ..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 ..
  52. pmc A highly conserved motif at the COOH terminus dictates endoplasmic reticulum exit and cell surface expression of NKCC2
    Nancy Zaarour
    INSERM, UMRS 872 Equipe 3 ERL7226, 75006 Paris, France
    J Biol Chem 284:21752-64. 2009
    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 ..
  53. pmc Cardiovascular expression of the mouse WNK1 gene during development and adulthood revealed by a BAC reporter assay
    Celine Delaloy
    INSERM, Unit 772, Paris, France
    Am J Pathol 169:105-18. 2006
    ..Despite this limitation, this transgenic model is a potentially valuable tool for the analysis of spatial and temporal aspects of WNK1 expression and regulation...
  54. ncbi Sequential expression of NKCC2, TonEBP, aldose reductase, and urea transporter-A in developing mouse kidney
    Hyun Wook Lee
    Department of Anatomy, College of Medicine, The Catholic University of Korea, Seoul
    Am J Physiol Renal Physiol 292:F269-77. 2007
    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 ..
  55. pmc Six2 is required for suppression of nephrogenesis and progenitor renewal in the developing kidney
    Michelle Self
    Department of Genetics and Tumor Cell Biology, St Jude Children s Research Hospital, Memphis, TN 38105 2794, USA
    EMBO J 25:5214-28. 2006
    ..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...
  56. ncbi Grainyhead-related transcription factor is required for duct maturation in the salivary gland and the kidney of the mouse
    Yoshifumi Yamaguchi
    Okazaki Institute for Integrative Biosciences, National Institutes of Natural Sciences, Myodaiji, Okazaki, 444 8787, Japan
    Development 133:4737-48. 2006
    ..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...
  57. ncbi 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)
    Ignacio Gimenez
    Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, Connecticut 06511, USA
    J Biol Chem 282:6540-7. 2007
    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 ..
  58. ncbi Renal function in mice with targeted disruption of the A isoform of the Na-K-2Cl co-transporter
    Mona Oppermann
    NIDDK, NIH, Building 10, Room 4 D51, 10 Center Drive MSC 1370, Bethesda, MD 20892 1370, USA
    J Am Soc Nephrol 18:440-8. 2007
    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...
  59. ncbi Screening for increased plasma urea levels in a large-scale ENU mouse mutagenesis project reveals kidney disease models
    Bernhard Aigner
    Institute of Molecular Animal Breeding and BiotechnologyInstitute of Molecular Animal Breeding and Biotechnology, Ludwig Maximilians University, Munich, Germany
    Am J Physiol Renal Physiol 292:F1560-7. 2007
    ....
  60. ncbi Pax2 and pax8 regulate branching morphogenesis and nephron differentiation in the developing kidney
    Melina Narlis
    McGill Cancer Centre and Biochemistry Department, McGill University, 3655 Promenade Sir William Osler, Montreal, Quebec H3G 1Y6, Canada
    J Am Soc Nephrol 18:1121-9. 2007
    ..Together, these results demonstrate a crucial role for Pax2 and Pax8 in nephron differentiation and branching morphogenesis of the metanephros...
  61. ncbi Norepinephrine, via beta-adrenoceptors, regulates bumetanide-sensitive cotransporter type 1 expression in thick ascending limb cells
    Prajakta A Sonalker
    Department of Pharmacology, Center for Clinical Pharmacology, University of Pittsburgh, School of Medicine, PA 15219, USA
    Hypertension 49:1351-7. 2007
    ....
  62. ncbi NKCC2 surface expression in mammalian cells: down-regulation by novel interaction with aldolase B
    Boubacar Benziane
    INSERM U652, 75006 Paris, France
    J Biol Chem 282:33817-30. 2007
    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...
  63. pmc Hoxd11 specifies a program of metanephric kidney development within the intermediate mesoderm of the mouse embryo
    Joshua W Mugford
    Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA
    Dev Biol 319:396-405. 2008
    ..This program maintains tubule forming progenitors and instructs a metanephric specific pattern of nephron differentiation...
  64. pmc Isoforms of renal Na-K-2Cl cotransporter NKCC2: expression and functional significance
    Hayo Castrop
    Physiologisches Institut der Universität Regensburg, Universitätsstr 31, D 93040 Regensburg, Germany
    Am J Physiol Renal Physiol 295:F859-66. 2008
    ..Although NKCC2 is encoded by a single gene (Slc12a1), differential splicing of the NKCC2 pre-mRNA results in the formation of several alternate transcripts...
  65. ncbi Cloning, embryonic expression, and alternative splicing of a murine kidney-specific Na-K-Cl cotransporter
    P Igarashi
    Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06520, USA
    Am J Physiol 269:F405-18. 1995
    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...
  66. pmc Pygo2 expands mammary progenitor cells by facilitating histone H3 K4 methylation
    Bingnan Gu
    Department of Biological Chemistry, University of California, Irvine, Irvine, CA 92697, USA
    J Cell Biol 185:811-26. 2009
    ....

Research Grants1

  1. Cux-1 and cell cycle regulation in kidney development
    Gregory Vanden Heuvel; Fiscal Year: 2009
    ..4. Define the relationship between Cux-1, TLE-4, and Notch signaling during podocyte development and nephrogenesis. These studies will provide novel insights into the mechanisms of cell proliferation during development. ..