Article ; Online: Transient receptor potential melastatin 6 knockout mice are lethal whereas heterozygous deletion results in mild hypomagnesemia.
2011 Volume 117, Issue 2, Page(s) p11–9
Abstract: ... lethal in mice. Heterozygous deletion of TRPM6 results in a mild hypomagnesemia. The Mg(2+)-enriched diet ... to characterize homozygous (-/-) and heterozygous (+/-) TRPM6 knockout mice with respect to Mg(2+) homeostasis ... magnesium (Mg(2+)) (re)absorption. The underlying defect is a mutation in the transient receptor potential ...
| Abstract | 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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| MeSH term(s) | Animals ; Calcium/urine ; Feces/chemistry ; Female ; Gene Deletion ; Gene Expression/physiology ; Genes, Lethal ; Genotype ; Heterozygote ; Magnesium/blood ; Magnesium/urine ; Magnesium Deficiency/blood ; Magnesium Deficiency/genetics ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Severity of Illness Index ; TRPM Cation Channels/genetics ; TRPM Cation Channels/metabolism |
| Chemical Substances | TRPM Cation Channels ; Trpm6 protein, mouse ; Magnesium (I38ZP9992A) ; Calcium (SY7Q814VUP) |
| Language | English |
| Publishing date | 2011 |
| Publishing country | Switzerland |
| Document type | Journal Article ; Research Support, Non-U.S. Gov't |
| ZDB-ID | 207121-6 |
| ISSN | 1660-2137 ; 1423-0186 ; 2235-3186 ; 1660-8151 ; 0028-2766 |
| ISSN (online) | 1660-2137 ; 1423-0186 ; 2235-3186 |
| ISSN | 1660-8151 ; 0028-2766 |
| DOI | 10.1159/000320580 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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