Severe Neurologic Impairment in Mice with Targeted Disruption of the Electrogenic Sodium Bicarbonate Cotransporter NBCe2 (Slc4a5 Gene)

Kao, Liyo; Kurtz, Lisa M; Shao, Xuesi M.; Papadopoulos, Marios C.; Liu, Li; Bok, Dean; Nusinowitz, Steven; Chen, Bryan; Stella, Salvatore; Andre, Mark; Weinreb, Josh; Luong, Serena S.; Piri, Natik; Kwong, Jessica Y. Y.; Newman, Debra K.; Kurtz, Ira

doi:10.1074/jbc.m111.249961

Cited by 66 publications

(83 citation statements)

References 64 publications

(62 reference statements)

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“…Targeted disruption of NBCe2 in mice also results in hypertension (15) or neurological dysfunction (20). These studies suggest that NBCe2 plays an important role in various other biological functions.…”

Section: Summary and Conclusion Genetic Studies In Humans Havementioning

confidence: 90%

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Deficient acid handling with distal RTA in the NBCe2 knockout mouse

Wen

Yuan

Cornelius

et al. 2015

American Journal of Physiology-Renal Physiology

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In the present study, we report that a mouse model lacking the electrogenic Na ϩ -HCO 3 Ϫ cotransporter [NBCe2/Slc4a5; NBCe2 knockout (KO) mice] developed dRTA after an oral acid challenge. NBCe2 expression was identified in the connecting tubule (CNT) of wild-type mice, and its expression was significantly increased after acid loading. NBCe2 KO mice did not have dRTA when on a standard mouse diet. However, after acid loading, NBCe2 KO mice exhibited complete features of dRTA, characterized by insufficient urinary acidification, hyperchloremic hypokalemic metabolic acidosis, and hypercalciuria. Additional experiments showed that NBCe2 KO mice had decreased luminal transepithelial potential in the CNT, as revealed by micropuncture. Further immunofluorescence and Western blot experiments found that NBCe2 KO mice had increased expression of H ϩ -ATPase B1 in the plasma membrane. These results showed that NBCe2 KO mice with acid loading developed increased urinary K ϩ and Ca 2ϩ wasting due to decreased luminal transepithelial potential in the CNT. NBCe2 KO mice compensated to maintain systemic pH by increasing H ϩ -ATPase in the plasma membrane.

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Section: Summary and Conclusion Genetic Studies In Humans Havementioning

confidence: 90%

“…The Slc4a5 gene encodes NBCe2; its expression has been identified in the choroid plexus (20), liver (1), and kidney (47). Electrophysiological studies have shown that NBCe2 mediates Na ϩ -HCO 3 Ϫ transport with a 1:2 or 1:3 stoichiometry and plays an important role in intracellular pH regulation (35,40).…”

Section: Discussionmentioning

confidence: 99%

Deficient acid handling with distal RTA in the NBCe2 knockout mouse

Wen

Yuan

Cornelius

et al. 2015

American Journal of Physiology-Renal Physiology

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“…This form is expressed predominantly in liver, spleen, and testis, but also in the kidney, stomach, lung, heart, and brain. SLC4A5 has been linked to hypertension and the slc4a5 mouse knockout exhibits hypertension, as well as dRTA, and vision and neurological defects (Groger et al, 2012;Kao et al, 2011).…”

Section: Sodium-bicarbonate Cotransportersmentioning

confidence: 99%

Structure, Function, and Trafficking of SLC4 and SLC26 Anion Transporters

Cordat

Reithmeier

2014

Current Topics in Membranes

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“…Recently, Kao et al. [13] demonstrated that the loss of NBC4 results in severe brain ventricular hypovolaemia and decreased intracranial pressure.…”

Section: Introductionmentioning

confidence: 99%

Identification and properties of a novel variant of NBC4 (Na+/HCO3− co-transporter 4) that is predominantly expressed in the choroid plexus

Fukuda

Hirata

Nakamura

et al. 2013

Biochemical Journal

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Secretion of HCO(3)- at the apical side of the epithelial cells of the choroid plexus is an essential step in the formation of cerebrospinal fluid. Anion conductance with a high degree of HCO(3)- permeability has been observed and suggested to be the major pathway for HCO(3)- transport across the apical membrane. Recently, it was found that NBC (Na(+)/HCO(3)- co-transporter) 4, an electrogenic member of the NBC family, was expressed in the choroid plexus. We found that a novel variant of the NBC4 [NBC4g/Slc4a5 (solute carrier family 4, sodium bicarbonate co-transporter, member 5)] is almost exclusively expressed in the apical membrane of rat choroid plexus epithelium at exceptionally high levels. RNA interference-mediated knockdown allowed the functional demonstration that NBC4g is the major player in the HCO(3)- transport across the apical membrane of the choroid plexus epithelium. When combined with a recent observation that in choroid plexus epithelial cells electrogenic NBC operates with a stoichiometry of 3:1, the results of the present study suggest that NBC4g mediates the efflux of HCO(3)- and contributes to cerebrospinal fluid production.

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Severe Neurologic Impairment in Mice with Targeted Disruption of the Electrogenic Sodium Bicarbonate Cotransporter NBCe2 (Slc4a5 Gene)

Cited by 66 publications

References 64 publications

Deficient acid handling with distal RTA in the NBCe2 knockout mouse

Deficient acid handling with distal RTA in the NBCe2 knockout mouse

Structure, Function, and Trafficking of SLC4 and SLC26 Anion Transporters

Identification and properties of a novel variant of NBC4 (Na+/HCO3− co-transporter 4) that is predominantly expressed in the choroid plexus

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