Histidinemia in mice: a metabolic defect treated using a novel approach to hepatocellular transplantation

Hepatology. 1995 May;21(5):1405-12.

Abstract

Histidinemia in mice and in humans is an autosomal recessive disorder of histidine metabolism that leads to high-histidine levels in both plasma and urine and is caused by a lack of hepatic histidine-alpha-deaminase (histidase). We have used a novel approach to hepatocellular transplantation to effect a complete phenotypic cure of histidinemia in a mouse model. Mice lacking histidase were treated with isolated liver cells (approximately 18 x 10(6) hepatocytes and 9 x 10(6) nonparenchymal cells) from histidase-competent donors transplanted into the peritoneum (active transplant group). Recipient mice showed a dramatic decrease, by more than 75%, in urinary histidine levels from day one throughout the course of the experiment, resulting in levels within the normal range for wild-type mice. In comparison, there was no change in urinary histidine levels in the control group of histidase-deficient mice treated with isolated liver cells from mice lacking histidase (statistical comparison between the two groups, P < .003, two-way ANOVA). Histologically, ectopic liver tissue was seen in the peritoneum in association with abdominal wall, pancreas, and peritoneal connective tissue; immunohistochemical evidence showed expression of histidase in the ectopic liver tissue in the active transplant group. This report is the first to show complete correction of a defective biochemical phenotype achieved by hepatocellular transplantation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Transplantation*
  • Histidine / blood*
  • Histidine / deficiency
  • Histidine / urine
  • Histidine Ammonia-Lyase / metabolism
  • Hybridization, Genetic
  • Immunohistochemistry / methods
  • Liver / cytology*
  • Liver / enzymology
  • Liver / pathology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred Strains
  • Staining and Labeling

Substances

  • Histidine
  • Histidine Ammonia-Lyase