Deletion of Trpm7 disrupts embryonic development and thymopoiesis without altering Mg2+ homeostasis.
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.
Jin
Jie
J
Department of Cardiology, Howard Hughes Medical Institute, Children's Hospital Boston, Boston, MA 02115, USA.
Desai
Bimal N
BN
Navarro
Betsy
B
Donovan
Adriana
A
Andrews
Nancy C
NC
Clapham
David E
DE
D000818:Animals; D047108:Embryonic Development; D017353:Gene Deletion; D006706:Homeostasis; D018960:Hyaluronan Receptors / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D038041:Lymphopoiesis; D008274:Magnesium / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D018408:Patch-Clamp Techniques; D050796:STAT3 Transcription Factor / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology / Q000378:metabolism*; D050053:TRPM Cation Channels / Q000235:genetics / Q000502:physiology*; D013950:Thymus Gland / Q000166:cytology*
D018960:Hyaluronan Receptors; D036341:Intercellular Signaling Peptides and Proteins; D053645:Interleukin-2 Receptor alpha Subunit; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D050053:TRPM Cation Channels; C421903:Trpm7 protein, mouse; D008274:Magnesium