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Science 322 (5902): 756-760

Copyright © 2008 by the American Association for the Advancement of Science

Deletion of Trpm7 Disrupts Embryonic Development and Thymopoiesis Without Altering Mg2+ Homeostasis

Jie Jin,1,2* Bimal N. Desai,1* Betsy Navarro,1 Adriana Donovan,2 Nancy C. Andrews,2,3 David E. Clapham1{dagger}

Abstract: 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 Mg2+ 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 Mg2+ or the maintenance of total cellular Mg2+. 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.

1 Department of Cardiology, Howard Hughes Medical Institute, Children's Hospital Boston, and Department of Neurobiology, Harvard Medical School, Enders Building 1309, 320 Longwood Avenue, Boston, MA 02115, USA.
2 Division of Hematology and Oncology, Children's Hospital Boston, Karp Family Building 8-125A, Boston, MA 02115, USA.
3 Department of Pediatrics and Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, NC 27702, USA.

* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: dclapham{at}enders.tch.harvard.edu

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