PMID- 24429824
OWN - NLM
STAT- MEDLINE
DCOM- 20140904
LR  - 20240320
IS  - 1421-9778 (Electronic)
IS  - 1015-8987 (Print)
IS  - 1015-8987 (Linking)
VI  - 32
IP  - 7
DP  - 2013
TI  - Double knockout of carbonic anhydrase II (CAII) and Na(+)-Cl(-) cotransporter 
      (NCC) causes salt wasting and volume depletion.
PG  - 173-83
LID - 10.1159/000356637 [doi]
AB  - BACKGROUND AND AIMS: The thiazide-sensitive Na(+)-Cl(-) cotransporter NCC and the 
      Cl(-)/HCO3(-)exchanger pendrin are expressed on apical membranes of distal 
      cortical nephron segments and mediate salt absorption, with pendrin working in 
      tandem with the epithelial Na(+) channel (ENaC) and the Na(+)-dependent 
      chloride/bicarbonate exchanger (NDCBE), whereas NCC is working by itself. A 
      recent study showed that NCC and pendrin compensate for loss of each other under 
      basal conditions, therefore masking the role that each plays in salt 
      reabsorption. Carbonic anhydrase II (CAII, CA2 or CAR2) plays an important role 
      in acid-base transport and salt reabsorption in the proximal convoluted tubule 
      and acid-base transport in the collecting duct. Animals with CAII deletion show 
      remodeling of intercalated cells along with the downregulation of pendrin. NCC KO 
      mice on the other hand show significant upregulation of pendrin and ENaC. Neither 
      model shows any significant salt wasting under baseline conditions. We 
      hypothesized that the up-regulation of pendrin is essential for the prevention of 
      salt wasting in NCC KO mice. METHODS AND RESULTS: To test this hypothesis, we 
      generated NCC/CAII double KO (dKO) mice by crossing mice with single deletion of 
      NCC and CAII. The NCC/CAII dKO mice displayed significant downregulation of 
      pendrin, along with polyuria and salt wasting. As a result, the dKO mice 
      developed volume depletion, which was associated with the inability to 
      concentrate urine. CONCLUSIONS: We conclude that the upregulation of pendrin is 
      essential for the prevention of salt and water wasting in NCC deficient animals 
      and its downregulation or inactivation will result in salt wasting, impaired 
      water conservation and volume depletion in the setting of NCC inactivation or 
      inhibition.
CI  - (c) 2014 S. Karger AG, Basel.
FAU - Xu, Jie
AU  - Xu J
AD  - Research Services, Veterans Affairs Medical Center, University of Cincinnati, 
      Cincinnati, OH, USA.
FAU - Barone, Sharon
AU  - Barone S
FAU - Brooks, Mary-Beth
AU  - Brooks MB
FAU - Soleimani, Manoocher
AU  - Soleimani M
LA  - eng
GR  - R01 DK062809/DK/NIDDK NIH HHS/United States
GR  - R56 DK062809/DK/NIDDK NIH HHS/United States
GR  - R56DK62809/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20131218
PL  - Germany
TA  - Cell Physiol Biochem
JT  - Cellular physiology and biochemistry : international journal of experimental 
      cellular physiology, biochemistry, and pharmacology
JID - 9113221
RN  - 0 (Anion Transport Proteins)
RN  - 0 (Chloride-Bicarbonate Antiporters)
RN  - 0 (Salts)
RN  - 0 (Slc12a3 protein, mouse)
RN  - 0 (Slc26a4 protein, mouse)
RN  - 0 (Solute Carrier Family 12, Member 3)
RN  - 0 (Sulfate Transporters)
RN  - 451W47IQ8X (Sodium Chloride)
RN  - EC 4.2.1.- (Carbonic Anhydrase II)
SB  - IM
MH  - Animals
MH  - Anion Transport Proteins/biosynthesis/*genetics
MH  - Carbonic Anhydrase II/genetics/*metabolism
MH  - Chloride-Bicarbonate Antiporters/metabolism
MH  - Gene Expression Regulation
MH  - Kidney Tubules, Collecting/*metabolism
MH  - Mice
MH  - Mice, Knockout
MH  - Polyuria/genetics/metabolism
MH  - Salts/urine
MH  - Sodium Chloride/metabolism
MH  - Solute Carrier Family 12, Member 3/biosynthesis/genetics/metabolism
MH  - Sulfate Transporters
PMC - PMC10947769
MID - NIHMS560952
EDAT- 2014/01/17 06:00
MHDA- 2014/09/05 06:00
PMCR- 2024/03/18
CRDT- 2014/01/17 06:00
PHST- 2013/11/21 00:00 [accepted]
PHST- 2014/01/17 06:00 [entrez]
PHST- 2014/01/17 06:00 [pubmed]
PHST- 2014/09/05 06:00 [medline]
PHST- 2024/03/18 00:00 [pmc-release]
AID - 000356637 [pii]
AID - 10.1159/000356637 [doi]
PST - ppublish
SO  - Cell Physiol Biochem. 2013;32(7):173-83. doi: 10.1159/000356637. Epub 2013 Dec 
      18.