Article ; Online: Deletion of Trpm7 disrupts embryonic development and thymopoiesis without altering Mg2+ homeostasis.
2008 Volume 322, Issue 5902, Page(s) 756–760
Abstract: ... 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 ... at the double-negative stage and a progressive depletion of thymic medullary cells. However, deletion of Trpm7 ...
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. |
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MeSH term(s) | Animals ; Embryonic Development ; Gene Deletion ; Homeostasis ; Hyaluronan Receptors/metabolism ; Intercellular Signaling Peptides and Proteins/genetics ; Intercellular Signaling Peptides and Proteins/metabolism ; Interleukin-2 Receptor alpha Subunit/metabolism ; Lymphopoiesis ; Magnesium/metabolism ; Mice ; Mice, Knockout ; Patch-Clamp Techniques ; STAT3 Transcription Factor/metabolism ; T-Lymphocytes/cytology ; T-Lymphocytes/immunology ; T-Lymphocytes/metabolism ; TRPM Cation Channels/genetics ; TRPM Cation Channels/physiology ; Thymus Gland/cytology | ||||||||||
Chemical Substances | Hyaluronan Receptors ; Intercellular Signaling Peptides and Proteins ; Interleukin-2 Receptor alpha Subunit ; STAT3 Transcription Factor ; Stat3 protein, mouse ; TRPM Cation Channels ; Trpm7 protein, mouse (EC 2.7.1.-) ; Magnesium (I38ZP9992A) | ||||||||||
Language | English | ||||||||||
Publishing date | 2008-10-22 | ||||||||||
Publishing country | United States | ||||||||||
Document type | Journal Article ; Research Support, N.I.H., Extramural | ||||||||||
ZDB-ID | 128410-1 | ||||||||||
ISSN | 1095-9203 ; 0036-8075 | ||||||||||
ISSN (online) | 1095-9203 | ||||||||||
ISSN | 0036-8075 | ||||||||||
DOI | 10.1126/science.1163493 | ||||||||||
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Database | MEDical Literature Analysis and Retrieval System OnLINE |
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