Transient receptor potential melastatin 6 knockout mice are lethal whereas heterozygous deletion results in mild hypomagnesemia
until further notice
SourceNephron Physiology, 117, 2, (2011), pp. 11-19
Article / Letter to editor
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SubjectNCMLS 5: Membrane transport and intracellular motility IGMD 9: Renal disorder
BACKGROUND: Hypomagnesemia with secondary hypocalcemia is due to disturbed renal and intestinal magnesium (Mg(2+)) (re)absorption. The underlying defect is a mutation in the transient receptor potential melastatin type 6 (TRPM6), a Mg(2+)-permeable ion channel expressed in the kidney and intestine. Our aim was to characterize homozygous (-/-) and heterozygous (+/-) TRPM6 knockout mice with respect to Mg(2+) homeostasis. METHODS: TRPM6(+/-) mice were bred on a normal (0.19% wt/wt Mg(2+)) and high (0.48% wt/wt Mg(2+)) Mg(2+) diet. In the offspring, 24-hour urinary Mg(2+) and calcium excretion as well as serum concentrations of both were determined. TRPM6 mRNA expression in the kidney and colon was measured. RESULTS: On the regular diet, 30% of the offspring were TRPM6 wild-type ((+/+)), 70% were TRPM6(+/-), and none were TRPM6(-/-). The genotypic distribution of the litters remained the same on the 0.48% Mg(2+) diet. In TRPM6(+/-) mice on both diets, serum Mg(2+) levels were significantly lower, and renal and intestinal TRPM6 mRNA expression was reduced. Urinary Mg(2+) excretion was unaffected. CONCLUSIONS: Homozygous TRPM6 deletion is embryonic lethal in mice. Heterozygous deletion of TRPM6 results in a mild hypomagnesemia. The Mg(2+)-enriched diet could not compensate for either embryonic lethality or hypomagnesemia caused by TRPM6 deficiency.
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