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http://purl.uniprot.org/citations/31040187http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/31040187http://www.w3.org/2000/01/rdf-schema#comment"

Background

The SLC4A4 gene encodes electrogenic sodium bicarbonate cotransporter 1 (NBCe1). Inheritance of recessive mutations in SLC4A4 causes proximal renal tubular acidosis (pRTA), a disease characterized by metabolic acidosis, growth retardation, ocular abnormalities, and often dental abnormalities. Mouse models of pRTA exhibit acidemia, corneal edema, weak dental enamel, impacted colons, nutritional defects, and a general failure to thrive, rarely surviving beyond weaning. Alkali therapy remains the preferred treatment for pRTA, but it is unclear which nonrenal signs are secondary to acidemia and which are a direct consequence of NBCe1 loss from nonrenal sites (such as the eye and enamel organ) and therefore require separate therapy. SLC4A4 encodes three major NBCe1 variants: NBCe1-A, NBCe1-B, and NBCe1-C. NBCe1-A is expressed in proximal tubule epithelia; its dysfunction causes the plasma bicarbonate insufficiency that underlies acidemia. NBCe1-B and NBCe1-C exhibit a broad extra-proximal-tubular distribution.

Methods

To explore the consequences of Nbce1b/c loss in the absence of acidemia, we engineered a novel strain of Nbce1b/c-null mice and assessed them for signs of pRTA.

Results

Nbce1b/c-null mice have normal blood pH, but exhibit increased mortality, growth retardation, corneal edema, and tooth enamel defects.

Conclusions

The correction of pRTA-related acidemia should not be considered a panacea for all signs of pRTA. The phenotype of Nbce1b/c-null mice highlights the physiologic importance of NBCe1 variants expressed beyond the proximal tubular epithelia and potential limitations of pH correction by alkali therapy in pRTA. It also suggests a novel genetic locus for corneal dystrophy and enamel hypomineralization without acidemia."xsd:string
http://purl.uniprot.org/citations/31040187http://purl.org/dc/terms/identifier"doi:10.1681/asn.2018050545"xsd:string
http://purl.uniprot.org/citations/31040187http://purl.uniprot.org/core/author"Marshall J."xsd:string
http://purl.uniprot.org/citations/31040187http://purl.uniprot.org/core/author"Parker M.D."xsd:string
http://purl.uniprot.org/citations/31040187http://purl.uniprot.org/core/author"Marshall A."xsd:string
http://purl.uniprot.org/citations/31040187http://purl.uniprot.org/core/author"Patel S.P."xsd:string
http://purl.uniprot.org/citations/31040187http://purl.uniprot.org/core/author"Alsufayan T."xsd:string
http://purl.uniprot.org/citations/31040187http://purl.uniprot.org/core/author"Mballo C.S.A."xsd:string
http://purl.uniprot.org/citations/31040187http://purl.uniprot.org/core/author"Quade B.N."xsd:string
http://purl.uniprot.org/citations/31040187http://purl.uniprot.org/core/author"Salerno E.E."xsd:string
http://purl.uniprot.org/citations/31040187http://purl.uniprot.org/core/date"2019"xsd:gYear
http://purl.uniprot.org/citations/31040187http://purl.uniprot.org/core/name"J Am Soc Nephrol"xsd:string
http://purl.uniprot.org/citations/31040187http://purl.uniprot.org/core/pages"979-989"xsd:string
http://purl.uniprot.org/citations/31040187http://purl.uniprot.org/core/title"Extrarenal Signs of Proximal Renal Tubular Acidosis Persist in Nonacidemic Nbce1b/c-Null Mice."xsd:string
http://purl.uniprot.org/citations/31040187http://purl.uniprot.org/core/volume"30"xsd:string
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