Intravital imaging of Ca2+ signals in lymphocytes of Ca2+ biosensor transgenic mice: Indication of autoimmune diseases before the pathological onset

Soichiro Yoshikawa, Takako Usami, Junichi Kikuta, Masaru Ishii, Tetsuo Sasano, Koji Sugiyama, Tetsushi Furukawa, Eiji Nakasho, Hiroshi Takayanagi, Thomas F. Tedder, Hajime Karasuyama, Atsushi Miyawaki, Takahiro Adachi

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Abstract

Calcium ion (Ca2+) signaling is a typical phenomenon mediated through immune receptors, such as the B-cell antigen receptor (BCR), and it is important for their biological activities. To analyze the signaling of immune receptors together with their in vivo dynamics, we generated stable transgenic mice with the Föster/fluorescence resonance energy transfer (FRET)-based Ca2+ indicator yellow cameleon 3.60 (YC3.60), based on the Cre/loxP system (YC3.60flox). We successfully obtained mice with specific YC3.60 expression in immune or nerve cells as well as mice with ubiquitous expression of this indicator. We established five-dimensional (5D) (x, y, z, time, and Ca2+) intravital imaging of lymphoid tissues, including the bone marrow. Furthermore, in autoimmune-prone models, the CD22-/- and C57BL/6- lymphoproliferation (lpr)/lpr mouse, Ca2+ fluxes were augmented, although they did not induce autoimmune disease. Intravital imaging of Ca2+ signals in lymphocytes may improve assessment of the risk of autoimmune diseases in model animals.

Original languageEnglish
Article number18738
JournalScientific reports
Volume6
DOIs
Publication statusPublished - Jan 6 2016
Externally publishedYes

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    Yoshikawa, S., Usami, T., Kikuta, J., Ishii, M., Sasano, T., Sugiyama, K., Furukawa, T., Nakasho, E., Takayanagi, H., Tedder, T. F., Karasuyama, H., Miyawaki, A., & Adachi, T. (2016). Intravital imaging of Ca2+ signals in lymphocytes of Ca2+ biosensor transgenic mice: Indication of autoimmune diseases before the pathological onset. Scientific reports, 6, [18738]. https://doi.org/10.1038/srep18738