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Acute Induction of Soft Tissue Calcification with Transient Hyperphosphatemia in the KK Mouse by Modification in Dietary Contents of Calcium, Phosphorus, and Magnesium

Biological Research Laboratories, Research and Development Division, Takeda Chemical Industries, Ltd., Osaka, Japan

Severe cardiac calcification developed spontaneously in hereditarily diabetic KK mice maintained on a stock diet. Feeding purified diets with various mineral compositions to the mice caused two types of acute and reproducible calcification. In the first type, induced by a diet low in magnesium and high in phosphorus, the heart and the kidney were the most severely affected with calcium contents of the tissues elevated, respectively, about 300- and 100-fold after 10 days. The rapid increase of tissue calcium level was first recognized in the kidney with a simultaneous rise in plasma inorganic phosphorus after 24 hours on the diet. Addition of magnesium or reduction of phosphorus in the diet completely prevented the development of all these changes. Another type of experimental calcification, induced by diets low in magnesium, phosphorus and calcium, was characterized primarily by cardiac calcification and by the absence of renal calcification. These diet-induced calcifications were not recognized in ICR, C57BL and CF1 mice. The present findings suggest that relative deficiency in magnesium is mainly responsible for the development of the tissue calcification in KK mice.