Oncotarget

Research Papers: Pathology:

Elevated dietary magnesium during pregnancy and postnatal life prevents ectopic mineralization in Enpp1asj mice, a model for generalized arterial calcification of infancy

Joshua Kingman, Jouni Uitto and Qiaoli Li _

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Oncotarget. 2017; 8:38152-38160. https://doi.org/10.18632/oncotarget.16687

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Abstract

Joshua Kingman1, Jouni Uitto1 and Qiaoli Li1

1 Department of Dermatology and Cutaneous Biology, The Sidney Kimmel Medical College, and the PXE International Center of Excellence in Research and Clinical Care, Thomas Jefferson University, Philadelphia, PA, USA

Correspondence to:

Qiaoli Li, email:

Keywords: mouse model, ectopic mineralization, maternal diet, magnesium, generalized arterial calcification of infancy, Pathology Section

Received: October 28, 2016 Accepted: March 16, 2017 Published: March 29, 2017

Abstract

Generalized arterial calcification of infancy (GACI) is an autosomal recessive disorder caused by mutations in the ENPP1 gene. It is characterized by mineralization of the arterial blood vessels, often diagnosed prenatally, and associated with death in early childhood. There is no effective treatment for this devastating disorder. We previously characterized the Enpp1asjmutant mouse as a model of GACI, and we have now explored the effect of elevated dietary magnesium (five-fold) in pregnant mothers and continuing for the first 14 weeks of postnatal life. The mothers were kept on either control diet or experimental diet supplemented with magnesium. Upon weaning at 4 weeks of age the pups were placed either on control diet or high magnesium diet. The degree of mineralization was assessed at 14 weeks of age by histopathology and a chemical calcium assay in muzzle skin, kidney and aorta. Mice placed on high magnesium diet showed little, if any, evidence of mineralization when their corresponding mothers were also placed on diet enriched with magnesium during pregnancy and nursing. The reduced ectopic mineralization in these mice was accompanied by increased calcium and magnesium content in the urine, suggesting that magnesium competes calcium-phosphate binding thereby preventing the mineral deposition. These results have implications for dietary management of pregnancies in which the fetus is suspected of having GACI. Moreover, augmenting a diet with high magnesium may be beneficial for other ectopic mineralization diseases, including nephrocalcinosis.


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