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別タイトル
HBV及びHCV感染症研究のための新たなTK-NOGベースヒト化マウスモデルの検討
著者
小酒 慶一
キーワード
Human hepatocyte chimeric mouse
TK-NOG mouse
uPA-SCID mouse
Hepatitis B virus
Hepatitis C virus
Human serum albumin
NDC
医学
抄録(英)
The immunodeficient mice transplanted with human hepatocytes are available for the study of the human hepatitis viruses. Recently, human hepatocytes were also successfully transplanted in herpes simplex virus type-1 thymidine kinase (TK)-NOG mice. In this study, we attempted to infect hepatitis virus in humanized TK-NOG mice and urokinase-type plasminogen activator-severe combined immunodeficiency (uPA-SCID) mice. TK-NOG mice were injected intraperitoneally with 6 mg/kg of ganciclovir (GCV), and transplanted with human hepatocytes. Humanized TK-NOG mice and uPA/SCID mice were injected with hepatitis B virus (HBV)- or hepatitis C virus (HCV)-positive human serum samples. Human hepatocyte repopulation index (RI) estimated from human serum albumin levels in TK-NOG mice correlated well with pre-transplantation serum ALT levels induced by ganciclovir treatment. All humanized TK-NOG and uPA-SCID mice injected with HBV infected serum developed viremia irrespective of lower replacement index. In contrast, establishment of HCV viremia was significantly more frequent in TK-NOG mice with low human hepatocyte RI (<70%) than uPA-SCID mice with similar RI. Frequency of mice spontaneously in early stage of viral infection experiment (8 weeks after injection) was similar in both TK-NOG mice and uPA-SCID mice. Effects of drug treatment with entecavir or interferon were similar in both mouse models. TK-NOG mice thus useful for study of hepatitis virus virology and evaluation of anti-viral drugs.
言語
日本語
NII資源タイプ
学位論文
広大資料タイプ
学位論文
DCMIタイプ
text
フォーマット
application/pdf
関連情報(references)
Keiichi Kosaka, Nobuhiko Hiraga, Michio Imamura, Satoshi Yoshimi, Eisuke Murakami, Takashi Nakahara, Yoji Honda, Atsushi Ono, Tomokazu Kawaoka, Masataka Tsuge, Hiromi Abe, C. Nelson Hayes, Daiki Miki, Hiroshi Aikata, Hidenori Ochi, Yuji Ishida, Chise Tateno, Katsutoshi Yoshizato, Tamito Sasaki and Kazuaki Chayama; A novel TK-NOG based humanized mouse model for the study of HBV and HCV infections; Biochemical and Biophysical Research Communications, Volume 441, Issue 1, 8 November 2013, Pages 230-235 (doi: 10.1016/j.bbrc.2013.10.040)
関連情報URL(references)
http://doi.org/10.1016/j.bbrc.2013.10.040
学位記番号
甲第6380号
授与大学
広島大学(Hiroshima University)
学位名
博士(医学)
学位名の英名
Philosophy in Medical Science
学位の種類の英名
doctoral
学位授与年月日
2014-03-23
部局名
医歯薬学総合研究科



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