Funding outcome

Magnesium is essential for healthy nerve, muscle, immune, heart, and bone function. Even small changes in magnesium levels can cause noticeable health effects, including muscle cramps, fatigue, irregular heart rhythms, and problems with bone strength. Because so many systems depend on magnesium, the body must tightly regulate how much is kept in the bloodstream. This balance is achieved through a coordinated process involving diet, the intestine, bone, and the kidney. We obtain magnesium from food, we absorb part of it through the gut, we store a large portion in our bones, and the kidney decides how much magnesium to remove or keep. The kidney plays a particularly important role because whatever magnesium enters the urine may be permanently lost from the body. One part of the kidney, called the proximal tubule, reabsorbs a significant amount of magnesium before it reaches the bladder. However, scientists still do not know how magnesium crosses this part of the kidney. Identifying this pathway is important because magnesium disorders are common in both children and adults, yet treatment options remain limited. Our lab team recently discovered two proteins, claudin-2 and claudin-12, that help the kidney reabsorb calcium in the proximal tubule. Since magnesium and calcium share similar chemical properties, we propose that these same proteins may also control magnesium reabsorption. To test this idea, we will study mice that are genetically modified so they lack claudin-2, claudin-12, or both. We will measure magnesium levels in the blood, urine, and stool to determine whether these proteins are required to maintain healthy magnesium balance. By defining how the kidney handles magnesium at a molecular level, this project could lay the groundwork for improving the diagnosis and treatment of magnesium disorders in the future.