| First Author | Woudenberg-Vrenken TE | Year | 2011 |
| Journal | Nephron Physiol | Volume | 117 |
| Issue | 2 | Pages | p11-9 |
| PubMed ID | 20814221 | Mgi Jnum | J:210798 |
| Mgi Id | MGI:5571839 | Doi | 10.1159/000320580 |
| Citation | Woudenberg-Vrenken TE, et al. (2011) Transient receptor potential melastatin 6 knockout mice are lethal whereas heterozygous deletion results in mild hypomagnesemia. Nephron Physiol 117(2):p11-9 |
| abstractText | 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. |
