TY - JOUR
T1 - Intravital imaging of Ca2+ signals in lymphocytes of Ca2+ biosensor transgenic mice
T2 - Indication of autoimmune diseases before the pathological onset
AU - Yoshikawa, Soichiro
AU - Usami, Takako
AU - Kikuta, Junichi
AU - Ishii, Masaru
AU - Sasano, Tetsuo
AU - Sugiyama, Koji
AU - Furukawa, Tetsushi
AU - Nakasho, Eiji
AU - Takayanagi, Hiroshi
AU - Tedder, Thomas F.
AU - Karasuyama, Hajime
AU - Miyawaki, Atsushi
AU - Adachi, Takahiro
N1 - Funding Information:
We are grateful to Dr. K. Rajewsky (Max Delbrück Center for Molecular Medicine) for the CD19-Cre mice, Dr. M. Okada (Osaka University) for the CAG-Cre mice, G. Schütz (DKFZ) for the nestin-Cre mice, Dr. M. Matsuda (Kyoto University), Ms. M. Kasaoka (Osaka University) for 2P microscopy analysis and K. Mizuno, T. Asano, A. Ogawa, K. Saito, and A. Yamasaki for technical assistance. This work was supported in part by grants from the Ministry of Education, Culture, Sports, Science, and Technology of Japan, the Futaba Electronics Memorial Foundation, the All Japan Coffee Association, the Mishima Kaiun Memorial Foundation, and Yamada Research Grant.
Publisher Copyright:
© 2016, Nature Publishing Group. All rights reserved.
PY - 2016/1/6
Y1 - 2016/1/6
N2 - 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.
AB - 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.
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U2 - 10.1038/srep18738
DO - 10.1038/srep18738
M3 - Article
C2 - 26732477
AN - SCOPUS:84953234681
SN - 2045-2322
VL - 6
JO - Scientific Reports
JF - Scientific Reports
M1 - 18738
ER -