Haploinsufficiency of the Mouse Atp6v1b1 Gene Leads to a Mild Acid-Base Disturbance with Implications for Kidney Stone Disease
Background/Aims: Homozygous mutations or deletion of the ATP6V1B1 gene encoding for the B1 subunit of the vacuolar H+-ATPase leads to distal renal tubular acidosis in man and mice. In humans, heterozygous carriers of B1 mutations can develop incomplete dRTA with nephroclacinosis. Here, we investigat...
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| Format: | Article |
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Cell Physiol Biochem Press GmbH & Co KG
2018-05-01
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| Series: | Cellular Physiology and Biochemistry |
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| Online Access: | https://www.karger.com/Article/FullText/490186 |
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| author | Soline Bourgeois Carla Bettoni Stéphanie Baron Carsten A. Wagner |
| author_facet | Soline Bourgeois Carla Bettoni Stéphanie Baron Carsten A. Wagner |
| author_sort | Soline Bourgeois |
| collection | DOAJ |
| description | Background/Aims: Homozygous mutations or deletion of the ATP6V1B1 gene encoding for the B1 subunit of the vacuolar H+-ATPase leads to distal renal tubular acidosis in man and mice. In humans, heterozygous carriers of B1 mutations can develop incomplete dRTA with nephroclacinosis. Here, we investigated whether Atp6v1b1+/- mice also develop acid-base disturbances during an HCl acid load. Methods: We subjected Atp6v1b1+/+, Atp6v1b1+/-, Atp6v1b1-/- to an HCl-load for 7 days and investigated acid-base status, kidney function, and expression of renal acid-base transport proteins. Results: Atp6v1b1-/- mice had more alkaline urine and low ammoniuria, whereas Atp6v1b1+/- mice showed no difference in their urine parameters but higher blood chloride and lower blood pCO2 compared to controls. Subcellular localization of a4 and B2 subunits of H+-ATPase were unchanged within the 3 genotypes and Atp6v1b1+/+ and Atp6v1b1+/- mice exhibited a similar luminal localization of B1 subunit in intercalated cells. However, B1, B2 and a4 expression were decreased in renal membrane fractions from Atp6v1b1+/- mice compared to Atp6v1b1+/+ while B2 and a4 were unchanged and B1 protein was reduced in Atp6v1b+-/- kidneys. Compensatory mechanisms of B1 ablation were found only in the collecting duct with a down-regulation of pendrin in Atp6v1b1-/- mice. Conclusions: In conclusion, 1) Atp6v1b1+/- mice developed a mild incomplete dRTA. dRTA is partly compensated by respiration. 2) Compensatory mechanisms for the absence of B1 take place only in the collecting duct of Atp6v1b1-/- kidneys. |
| first_indexed | 2024-12-19T13:34:21Z |
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| issn | 1015-8987 1421-9778 |
| language | English |
| last_indexed | 2024-12-19T13:34:21Z |
| publishDate | 2018-05-01 |
| publisher | Cell Physiol Biochem Press GmbH & Co KG |
| record_format | Article |
| series | Cellular Physiology and Biochemistry |
| spelling | doaj.art-af1f4c7d1ed84158ad79c6ea3adc8f5d2022-12-21T20:19:15ZengCell Physiol Biochem Press GmbH & Co KGCellular Physiology and Biochemistry1015-89871421-97782018-05-014731095110710.1159/000490186490186Haploinsufficiency of the Mouse Atp6v1b1 Gene Leads to a Mild Acid-Base Disturbance with Implications for Kidney Stone DiseaseSoline BourgeoisCarla BettoniStéphanie BaronCarsten A. WagnerBackground/Aims: Homozygous mutations or deletion of the ATP6V1B1 gene encoding for the B1 subunit of the vacuolar H+-ATPase leads to distal renal tubular acidosis in man and mice. In humans, heterozygous carriers of B1 mutations can develop incomplete dRTA with nephroclacinosis. Here, we investigated whether Atp6v1b1+/- mice also develop acid-base disturbances during an HCl acid load. Methods: We subjected Atp6v1b1+/+, Atp6v1b1+/-, Atp6v1b1-/- to an HCl-load for 7 days and investigated acid-base status, kidney function, and expression of renal acid-base transport proteins. Results: Atp6v1b1-/- mice had more alkaline urine and low ammoniuria, whereas Atp6v1b1+/- mice showed no difference in their urine parameters but higher blood chloride and lower blood pCO2 compared to controls. Subcellular localization of a4 and B2 subunits of H+-ATPase were unchanged within the 3 genotypes and Atp6v1b1+/+ and Atp6v1b1+/- mice exhibited a similar luminal localization of B1 subunit in intercalated cells. However, B1, B2 and a4 expression were decreased in renal membrane fractions from Atp6v1b1+/- mice compared to Atp6v1b1+/+ while B2 and a4 were unchanged and B1 protein was reduced in Atp6v1b+-/- kidneys. Compensatory mechanisms of B1 ablation were found only in the collecting duct with a down-regulation of pendrin in Atp6v1b1-/- mice. Conclusions: In conclusion, 1) Atp6v1b1+/- mice developed a mild incomplete dRTA. dRTA is partly compensated by respiration. 2) Compensatory mechanisms for the absence of B1 take place only in the collecting duct of Atp6v1b1-/- kidneys.https://www.karger.com/Article/FullText/490186Distal renal tubular acidosisHeterozygosityCollecting duct |
| spellingShingle | Soline Bourgeois Carla Bettoni Stéphanie Baron Carsten A. Wagner Haploinsufficiency of the Mouse Atp6v1b1 Gene Leads to a Mild Acid-Base Disturbance with Implications for Kidney Stone Disease Cellular Physiology and Biochemistry Distal renal tubular acidosis Heterozygosity Collecting duct |
| title | Haploinsufficiency of the Mouse Atp6v1b1 Gene Leads to a Mild Acid-Base Disturbance with Implications for Kidney Stone Disease |
| title_full | Haploinsufficiency of the Mouse Atp6v1b1 Gene Leads to a Mild Acid-Base Disturbance with Implications for Kidney Stone Disease |
| title_fullStr | Haploinsufficiency of the Mouse Atp6v1b1 Gene Leads to a Mild Acid-Base Disturbance with Implications for Kidney Stone Disease |
| title_full_unstemmed | Haploinsufficiency of the Mouse Atp6v1b1 Gene Leads to a Mild Acid-Base Disturbance with Implications for Kidney Stone Disease |
| title_short | Haploinsufficiency of the Mouse Atp6v1b1 Gene Leads to a Mild Acid-Base Disturbance with Implications for Kidney Stone Disease |
| title_sort | haploinsufficiency of the mouse atp6v1b1 gene leads to a mild acid base disturbance with implications for kidney stone disease |
| topic | Distal renal tubular acidosis Heterozygosity Collecting duct |
| url | https://www.karger.com/Article/FullText/490186 |
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