Journal
SCIENCE
Volume 322, Issue 5902, Pages 756-760Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.1163493
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Funding
- NIH [T32HL007572-20]
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The gene transient receptor potential- melastatin- like 7 ( Trpm7) encodes a protein that functions as an ion channel and a kinase. TRPM7 has been proposed to be required for cellular Mg(2+) homeostasis in vertebrates. Deletion of mouse Trpm7 revealed that it is essential for embryonic development. Tissue- specific deletion of Trpm7 in the T cell lineage disrupted thymopoiesis, which led to a developmental block of thymocytes at the double- negative stage and a progressive depletion of thymic medullary cells. However, deletion of Trpm7 in T cells did not affect acute uptake of Mg(2+) or the maintenance of total cellular Mg(2+). Trpm7- deficient thymocytes exhibited dysregulated synthesis of many growth factors that are necessary for the differentiation and maintenance of thymic epithelial cells. The thymic medullary cells lost signal transducer and activator of transcription 3 activity, which accounts for their depletion when Trpm7 is disrupted in thymocytes.
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