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Sci Rep. 2016 Jan 6;6:18738. doi: 10.1038/srep18738.

Intravital imaging of Ca(2+) signals in lymphocytes of Ca(2+) biosensor transgenic mice: indication of autoimmune diseases before the pathological onset.

Author information

1
Department of Immune Regulation, Tokyo Medical and Dental University, Tokyo, 113-8519, Japan.
2
Laboratory of recombinant animals, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, 101-0062, Japan.
3
Immunology and Cell Biology, Graduate School of Medicine, Osaka University, Suita 565-0871, Japan.
4
Department of Biofunctional Informatics, Tokyo Medical and Dental University, Tokyo 113-8519, Japan.
5
Department of Bio-informational Pharmacology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo 113-8510, Japan.
6
R&D Group, Scientific Solutions Product Development Division, Olympus Corporation, Hachioji-shi, Tokyo 192-8507, Japan.
7
Department of Immunology, Graduate School of Medicine and Faculty of Medicine, The University of Tokyo, Tokyo 113-0033, Japan.
8
Department of Immunology, Duke University Medical Center, Durham, NC 27710.
9
Laboratory for Cell Function and Dynamics, Advanced Technology Development Group, Brain Science Institute, RIKEN, Wako, Saitama 351-0198, Japan.
10
Department of Immunology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, 113-8510, Japan.

Abstract

Calcium ion (Ca(2+)) 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 Ca(2+) indicator yellow cameleon 3.60 (YC3.60), based on the Cre/loxP system (YC3.60(flox)). 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 Ca(2+)) intravital imaging of lymphoid tissues, including the bone marrow. Furthermore, in autoimmune-prone models, the CD22(-/-) and C57BL/6- lymphoproliferation (lpr)/lpr mouse, Ca(2+) fluxes were augmented, although they did not induce autoimmune disease. Intravital imaging of Ca(2+) signals in lymphocytes may improve assessment of the risk of autoimmune diseases in model animals.

PMID:
26732477
PMCID:
PMC4702216
DOI:
10.1038/srep18738
[Indexed for MEDLINE]
Free PMC Article

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