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Decreasing liver manganese via dietary treatment corrects manganese excess, erythropoietin excess, and polycythemia in Slc30a10-deficient mice

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Abstract:
Manganese is an essential nutrient to the human body and is required for proper function. However, an excess of manganese can be toxic. The regulation of manganese levels in the body is transporter-dependent, with the Slc30a10 metal transporter responsible for excretion of manganese from liver hepatocytes into the bile. Mutations in the Slc30a10 gene resulting in Slc30a10 deficiency cause severe manganese excess. Our lab previously generated mutant mice with Slc30a10 deficiency which developed manganese excess due to impaired manganese excretion. These mice also developed polycythemia, a condition of abnormally high levels of red blood cells, and an excess of erythropoietin (Epo), a hormone normally produced in the kidneys that stimulates synthesis of red blood cells. Mutant mice had increased liver Epo RNA levels but decreased kidney Epo RNA levels, suggesting that the liver is the site of Epo production in mutant mice. To determine if liver manganese excess causes liver Epo excess and polycythemia in Slc30a10-deficient mice, wild-type and Slc30a10-deficient mice were raised on manganese-sufficient and -deficient diets and analyzed for liver manganese levels, liver Epo RNA levels, and red blood cell counts. In mutant mice, the manganese-deficient diet resulted in lower liver manganese levels, liver Epo RNA levels, and red blood cell counts. This suggests that decreasing liver manganese via dietary treatment corrected the manganese excess, Epo excess, and polycythemia in mutant mice. Overall, the results provide evidence that manganese excess causes liver Epo RNA excess and polycythemia in Slc30a10-deficient mice.

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Citation

Zhang, Jared, and Milankumar Prajapati, Heather Conboy, Tom Bartnikas, "Decreasing liver manganese via dietary treatment corrects manganese excess, erythropoietin excess, and polycythemia in Slc30a10-deficient mice" (2021). Summer Research Symposium. Brown Digital Repository. Brown University Library. https://doi.org/10.26300/gktp-6p57

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  • Summer Research Symposium

    Each year, Brown University showcases the research of its undergraduates at the Summer Research Symposium. More than half of the student-researchers are UTRA recipients, while others receive funding from a variety of Brown-administered and national programs and fellowships and go …
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