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Animal Bioresource in Japan

.: Home > Animal Bioresource in Japan > 2014 > Volume 63 Number 3 > Etsuko Fujii, Atsuhiko Kato, Yu Jau Chen, Koichi Matsubara, Yasuyuki Ohnishi, Masami Suzuki

Characterization of EBV-related Lymphoproliferative Lesions Arising in Donor Lymphocytes of Transplanted Human Tumor Tissues in the NOG Mouse

Etsuko Fujii, Atsuhiko Kato, Yu Jau Chen, Koichi Matsubara, Yasuyuki Ohnishi, Masami Suzuki
1)Research Division, Chugai Pharmaceutical Co., Ltd., 200 Kajiwara, Kamakura, Kanagawa 247-8530, Japan 2)Chugai Pharmabody Research, Pte. Ltd., 3 Biopolis Drive, #04-11 Synapse, 138623 Singapore 3)Pharma Logicals Research, Pte. Ltd., 11 Biopolis Way, #05-08/09 Helios, 138667 Singapore 4)Central Institute for Experimental Animals, 3-25-12 Tonomachi, Kawasaki-ku, Kawasaki, Kanagawa 210-0821, Japan
Abstract :

Human tumor tissue line models established in the severely immunodeficient NOD.Cg-Prkdcscid Il2rgtm1Sug/Jic (NOD/Shi-scid, IL-2Rγnull or NOG) mouse are important tools for oncology research. During the establishment process, a lymphoproliferative lesion (LPL) that replaces the original tumor cells in the site of transplantation occurs. In the present study, we studied the impact of the LPL on the establishment process and the characteristics of the lesion, investigated the systemic distribution of the lesion in the mouse, and evaluated the potential of a simple identification method. The incidence of the lesion varied among tumor types, and the lesion was found to be the leading cause of unsuccessful establishment with gastric and colorectal cancer. The lesion consisted of a varying population of proliferating lymphoid cells that expressed CD20. The cells were positive for Epstein-Barr virus (EBV)-related antigens, and EBV DNA was detected. There was systemic distribution of the lesion within the NOG mouse, and the most consistent gross finding was splenomegaly. Additionally, identification of LPL-affected cases was possible by detecting splenomegaly in the 1st and 2nd generation mice at necropsy. From our findings the lesion was judged to arise from EBV-infected B cells originating from the donor, and monitoring splenomegaly at necropsy was thought effective as a simple method for identifying the lesion at an early stage of the establishment process.

Keywords :
donor tissue, Epstein-Barr virus, lymphoproliferative lesion, NOG mouse

Date Deposited : 07 Apr 2015 10:21

Last Modified : 07 Apr 2015 10:21

Official URL: http://

Volume 63, Number 3, - 2014

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