OMG · OIT3: A novel Magnesiotropic Gene in Kidney

OIT3: A novel Magnesiotropic Gene in Kidney

Magnesium. is the second most abundant intracellular cation after potassium and it plays an essential role in the human body. Magnesium. serves as a cofactor in more than 600 enzymatic reactions that are crucial for life. Approximately 30-50% of dietary magnesium is absorbed by the intestines, subsequently reaching the blood stream to act on different organs or get stored in bones. Finally, the kidney will determine the final excretion in a tightly regulated process. Alterations in magnesium balance are associated with several diseases. Hypomagnesemia (serum Mg2+ levels below 0.70 mmol/L) or magnesium deficiency is the most common form of magnesium disturbance and it can be due to impaired intestinal magnesium absorption or renal loss of magnesium. Remarkably, hypomagnesemia is associated with highly prevalent metabolic disorders (e.g. diabetes, metabolic syndrome). In the past, some genetic causes of hypomagnesemia and renal magnesium wasting (increased loss of magnesium through the urine) have been identified in humans, encompassing mutations in magnesiotropic genes. This enables us to decipher the mechanisms involved in magnesium transport and kidney (patho)physiology. To date, many cases of magnesium disturbances (e.g. seen in metabolic disease) cannot be explained with the current knowledge, meaning that there is a clinical need to further elucidate the mechanisms underlying hypomagnesemia to find an effective treatment. Recently, we have identified several genes linked to kidney function in mice. Interestingly, one of the genes identified (Oit3) was associated with variations in urinary magnesium excretion. However, the mechanisms by which Oit3 regulates magnesium balance and its physiological relevance are unknown. Thanks to preliminary results we hypothesized that OIt3 regulates magnesium handling by modulating key magnesium transporters or proteins associated to magnesium balance in the kidney. The aim of the present project is to decipher the function of Oit3 on magnesium balance and unravel the molecular mechanisms by which it regulates magnesium handling. The overall objectives of this project are to understand the physiological role of our gene of interest in magnesium balance in a mice model and unravel the molecular mechanisms using a cell model by doing a functional characterization of the impact of this gene on magnesium transport and the interactions with ion channels and transporters.

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