Complete reconstitution of mouse liver with xenogeneic hepatocytes

Proc Natl Acad Sci U S A. 1995 May 23;92(11):4942-6. doi: 10.1073/pnas.92.11.4942.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Base Sequence
  • Cell Transplantation*
  • DNA / analysis
  • Female
  • Immunohistochemistry
  • Liver / cytology*
  • Liver / physiology
  • Liver Regeneration*
  • Male
  • Mice
  • Mice, Nude
  • Mice, Transgenic
  • Molecular Sequence Data
  • Oligonucleotide Probes
  • RNA, Messenger / analysis
  • Rats
  • Rats, Sprague-Dawley
  • Recombinant Fusion Proteins / biosynthesis
  • Serum Albumin / biosynthesis
  • Serum Albumin / genetics
  • Transferrin / analysis
  • Transferrin / biosynthesis
  • Transplantation, Heterologous*
  • Urokinase-Type Plasminogen Activator / biosynthesis
  • Urokinase-Type Plasminogen Activator / genetics

Substances

  • Oligonucleotide Probes
  • RNA, Messenger
  • Recombinant Fusion Proteins
  • Serum Albumin
  • Transferrin
  • DNA
  • Urokinase-Type Plasminogen Activator