title: Intravital imaging of Ca(2+) signals in lymphocytes of Ca(2+) biosensor transgenic mice: indication of autoimmune diseases before the pathological onset.
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.
authors.affiliation: Department of Immune Regulation, Tokyo Medical and Dental University, Tokyo, 113-8519, Japan.
authors.forename: Soichiro
authors.initials: S
authors.lastname: Yoshikawa
authors.affiliation: Laboratory of recombinant animals, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, 101-0062, Japan.
authors.forename: Takako
authors.initials: T
authors.lastname: Usami
authors.affiliation: Immunology and Cell Biology, Graduate School of Medicine, Osaka University, Suita 565-0871, Japan.
authors.forename: Junichi
authors.initials: J
authors.lastname: Kikuta
authors.affiliation: Immunology and Cell Biology, Graduate School of Medicine, Osaka University, Suita 565-0871, Japan.
authors.forename: Masaru
authors.initials: M
authors.lastname: Ishii
authors.affiliation: Department of Biofunctional Informatics, Tokyo Medical and Dental University, Tokyo 113-8519, Japan.
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Sasano
authors.affiliation: Department of Bio-informational Pharmacology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo 113-8510, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Sugiyama
authors.affiliation: Department of Bio-informational Pharmacology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo 113-8510, Japan.
authors.forename: Tetsushi
authors.initials: T
authors.lastname: Furukawa
authors.affiliation: R&D Group, Scientific Solutions Product Development Division, Olympus Corporation, Hachioji-shi, Tokyo 192-8507, Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Nakasho
authors.affiliation: Department of Immunology, Graduate School of Medicine and Faculty of Medicine, The University of Tokyo, Tokyo 113-0033, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Takayanagi
authors.affiliation: Department of Immunology, Duke University Medical Center, Durham, NC 27710.
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Tedder
authors.affiliation: Department of Immune Regulation, Tokyo Medical and Dental University, Tokyo, 113-8519, Japan.
authors.forename: Hajime
authors.initials: H
authors.lastname: Karasuyama
authors.affiliation: Laboratory for Cell Function and Dynamics, Advanced Technology Development Group, Brain Science Institute, RIKEN, Wako, Saitama 351-0198, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Miyawaki
authors.affiliation: Department of Immunology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, 113-8510, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Adachi
mesh_terms: D000818:Animals; D018941:Antigens, CD19 / Q000235:genetics / Q000378:metabolism; D001327:Autoimmune Diseases / Q000235:genetics / Q000378:metabolism; D015551:Autoimmunity; D015374:Biosensing Techniques / Q000379:methods*; D001853:Bone Marrow / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling; D004195:Disease Models, Animal; D015870:Gene Expression; D017930:Genes, Reporter; D008214:Lymphocytes / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D057054:Molecular Imaging / Q000379:methods*; D010581:Peyer's Patches / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D013154:Spleen / Q000378:metabolism
chemical_list: D018941:Antigens, CD19; D011993:Recombinant Fusion Proteins; D002118:Calcium