Establishment of a humanized model of liver using NOD/Shi-scid IL2Rgnull mice.
Severely immunodeficient NOD/Shi-scid IL2Rg(null) (NOG) mice are used as recipients for human tissue transplantation, which produces chimeric mice with various types of human tissue. NOG mice expressing transgenic urokinase-type plasminogen activator in the liver (uPA-NOG) were produced. Human hepatocytes injected into uPA-NOG mice repopulated the recipient livers with human cells. The uPA-NOG model has several advantages over previously produced chimeric mouse models of human liver: (1) the severely immunodeficient NOG background enables higher xenogeneic cell engraftment; (2) the absence of neonatal lethality enables mating of homozygotes, which increased the efficacy of homozygote production; and (3) donor xenogeneic human hepatocytes could be readily transplanted into young uPA-NOG mice, which provide easier surgical manipulation and improved recipient survival.
Suemizu
Hiroshi
H
Biomedical Research Department, Central Institute for Experimental Animals, 1430 Nogawa, Miyamae, Kawasaki, Kanagawa, Japan. suemizu@ciea.or.jp
Hasegawa
Masami
M
Kawai
Kenji
K
Taniguchi
Kenji
K
Monnai
Makoto
M
Wakui
Masatoshi
M
Suematsu
Makoto
M
Ito
Mamoru
M
Peltz
Gary
G
Nakamura
Masato
M
D000818:Animals; D002454:Cell Differentiation; D022781:Hepatocytes / Q000378:metabolism / Q000637:transplantation; D006801:Humans; D053645:Interleukin-2 Receptor alpha Subunit / Q000235:genetics; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D016031:Liver Transplantation; D051379:Mice; D008822:Mice, Transgenic; D023421:Models, Animal; D004364:Pharmaceutical Preparations / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology; D014183:Transplantation, Heterologous; D014568:Urokinase-Type Plasminogen Activator / Q000235:genetics
C508018:Il2ra protein, mouse; D053645:Interleukin-2 Receptor alpha Subunit; D004364:Pharmaceutical Preparations; D014568:Urokinase-Type Plasminogen Activator