Complete reconstitution of mouse liver with xenogeneic hepatocytes.
We have developed a system for studying hepatocellular growth potential in which liver cells are introduced into the diseased livers of albumin-urokinase (Alb-uPA) transgenic mice. To use this system to study xenogeneic cell transplantation, rat liver cells were introduced into immunotolerant Alb-uPA transgenic mice. In regenerated recipient livers, up to 100% of hepatocellular gene expression was of rat origin, demonstrating the creation of a functional mouse liver in which parenchyma is derived from xenogeneic (rat) hepatocytes. Immunotolerant Alb-uPA transgenic mice provide a tool for studying hepatocellular biology of any species, including humans, in a controlled experimental setting.
Rhim
J A
JA
Department of Animal Biology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia 19104, USA.
Sandgren
E P
EP
Palmiter
R D
RD
Brinster
R L
RL
D000818:Animals; D001483:Base Sequence; D017690:Cell Transplantation; D004247:DNA / Q000032:analysis; D005260:Female; D007150:Immunohistochemistry; D008099:Liver / Q000166:cytology* / Q000502:physiology; D008115:Liver Regeneration; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D012709:Serum Albumin / Q000096:biosynthesis / Q000235:genetics; D014168:Transferrin / Q000032:analysis / Q000096:biosynthesis; D014183:Transplantation, Heterologous; D014568:Urokinase-Type Plasminogen Activator / Q000096:biosynthesis / Q000235:genetics
D015345:Oligonucleotide Probes; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D012709:Serum Albumin; D014168:Transferrin; D004247:DNA; D014568:Urokinase-Type Plasminogen Activator