Complete reconstitution of mouse liver with xenogeneic hepatocytes

  1. J A Rhim,
  2. E P Sandgren,
  3. R D Palmiter, and
  4. R L Brinster
  1. Department of Animal Biology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia 19104, USA.

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.

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