Epithelial magnesium transport by TRPM6 is essential for prenatal development and adult survival
- Ludwig Maximilian University of Munich, Germany
- The University of Queensland, Australia
- Helmholtz Zentrum Munich, Germany
- German Institute of Human Nutrition, Germany
- Princeton Institute of Life Sciences, United States
- University of Würzburg, Germany
- LMU Munich, Germany
- Paracelsus Medical University, Austria
Abstract
Mg2+ regulates many physiological processes and signalling pathways. However, little is known about the mechanisms underlying the organismal balance of Mg2+. Capitalizing on a set of newly generated mouse models, we provide an integrated mechanistic model of the regulation of organismal Mg2+ balance during prenatal development and in adult mice by the ion channel TRPM6. We show that TRPM6 activity in the placenta and yolk sac is essential for embryonic development. In adult mice, TRPM6 is required in the intestine to maintain organismal Mg2+ balance, but is dispensable in the kidney. Trpm6 inactivation in adult mice leads to shortened lifespan, growth deficit and metabolic alterations indicative of impaired energy balance. Dietary Mg2+ supplementation not only rescues all phenotypes displayed by Trpm6-deficient adult mice, but also may extend the lifespan of wildtype mice. Hence, maintenance of organismal Mg2+ balance by TRPM6 is crucial for prenatal development and survival to adulthood.
Data availability
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Whole-genome profiling of the liver transcriptome in Trpm6 gene deficient mice and control littermatesPublicly available at the NCBI Gene Expression Omnibus (accession no: GSE70457).
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Data from: Epithelial magnesium transport by TRPM6 is essential for prenatal development and adult survivalAvailable at Dryad Digital Repository under a CC0 Public Domain Dedication.
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Ingenuity Pathway Analysis (IPA) analysis of hepatic transcripts altered in Trpm6-deficient miceAvailable at Dryad Digital Repository under a CC0 Public Domain Dedication.
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Metabolic profiling of the serum, liver and gastrocnemius muscle of Trpm6-deficient miceAvailable at Dryad Digital Repository under a CC0 Public Domain Dedication.
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MATLAB code used for statistical analysis of survival distributions of control and dietary treated miceAvailable at Dryad Digital Repository under a CC0 Public Domain Dedication.
Article and author information
Author details
Funding
Deutsche Forschungsgemeinschaft (TRR 152-P15)
- Vladimir Chubanov
Deutsche Forschungsgemeinschaft (TRP 152-P15)
- Thomas Gudermann
Deutsche Forschungsgemeinschaft (TRP 152-P14)
- Susanna Zierler
Deutsche Forschungsgemeinschaft (SFB1123-A1)
- Emiel PC van der Vorst
- Christian Weber
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Richard S Lewis, Stanford University School of Medicine, United States
Ethics
Animal experimentation: Experiments involving animals were done in accordance with the EU Animal Welfare Act and were approved by the local councils on animal care (permit No 55.2-1-54-2532-134-13 from Government of Oberbayern, Germany, and permit No 2347-15-2014 from State Ministry of Brandenburg, Germany).
Version history
- Received: August 25, 2016
- Accepted: December 13, 2016
- Accepted Manuscript published: December 19, 2016 (version 1)
- Version of Record published: January 6, 2017 (version 2)
Copyright
© 2016, Chubanov et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Epithelial magnesium transport by TRPM6 is essential for prenatal development and adult survival
eLife 5:e20914.
https://doi.org/10.7554/eLife.20914
