このエントリーをはてなブックマークに追加
ID 40621
file
Thumnail k6380_3.pdf 1.15 MB
Thumnail k6380_1.pdf 183 KB
Thumnail k6380_2.pdf 162 KB
title alternative
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
creator
Kosaka, Keiichi
subject
Human hepatocyte chimeric mouse
TK-NOG mouse
uPA-SCID mouse
Hepatitis B virus
Hepatitis C virus
Human serum albumin
NDC
Medical sciences
abstract
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.
language
jpn
nii type
Thesis or Dissertation
HU type
Doctoral Theses
DCMI type
text
format
application/pdf
relation 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)
relation references URL
http://doi.org/10.1016/j.bbrc.2013.10.040
grantid
甲第6380号
degreeGrantor
広島大学(Hiroshima University)
degreename Ja
博士(医学)
degreename En
Philosophy in Medical Science
degreelevel
doctoral
date of granted
2014-03-23
department
Graduate School of Biomedical Science



Last 12 months's access : ? times
Last 12 months's DL: ? times


This month's access: ? times
This month's DL: ? times