Genetic drivers of age-related changes in urinary magnesium excretion
(2024) Physiological Genomics — Vol. 56, n° 9, p. 634-647 (2024)
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- Authors
van Megen, Wouter H 
de Baaij, Jeroen H F Korstanje, Ron
- Abstract
- Although age-dependent alterations in urinary magnesium (Mg) excretion have been described, the underlying mechanism remains elusive. As heritability significantly contributes to variations in urinary Mg excretion, we measured urinary Mg excretion at different ages in a cohort of genetically variable Diversity Outbred (DO) mice. Compared with animals aged 6 mo, an increase in Mg excretion was observed at 12 and 18 mo. Quantitative trait locus (QTL) analysis revealed an association of a locus on chromosome 10 with Mg excretion at 6 mo of age, with (encoding oncoprotein-induced transcript 3; OIT3) as our primary candidate gene. To study the possible role of OIT3 in renal Mg handling, we generated and characterized knockout () mice. Although a slightly lower serum Mg concentration was present in male mice, this effect was not observed in female mice. In addition, urinary Mg excretion and the expression of renal magnesiotropic genes were unaltered in mice. For animals aged 12 and 18 mo, QTL analysis revealed an association with a locus on chromosome 19, which contains the gene encoding TRPM6, a known Mg channel involved in renal Mg reabsorption. Comparison with RNA sequencing (RNA-Seq) data revealed that mRNA expression is inversely correlated with the QTL effect, implying that TRPM6 may be involved in age-dependent changes in urinary Mg excretion in mice. In conclusion, we show here that variants in and are associated with urinary Mg excretion at distinct periods of life, although OIT3 is unlikely to affect renal Mg handling. Aging increased urinary magnesium (Mg) excretion in mice. We show here that variation in , a candidate gene for the locus associated with Mg excretion in young mice, is unlikely to be involved as knockout of did not affect Mg excretion. Differences in the expression of the renal Mg channel TRPM6 may contribute to the variation in urinary Mg excretion in older mice.
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Citations
van Megen, W. H., de Baaij, J. H. F., Churchill, G. A., Devuyst, O., Hoenderop, J. G. J., & Korstanje, R. (2024). Genetic drivers of age-related changes in urinary magnesium excretion. Physiological Genomics, 56(9), 634-647. https://doi.org/10.1152/physiolgenomics.00119.2023 (Original work published 2024)