HISTIDINEMIA IN MICE - A METABOLIC DEFECT TREATED USING A NOVEL-APPROACH TO HEPATOCELLULAR TRANSPLANTATION.
1405 - 1412.
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.
|Title:||HISTIDINEMIA IN MICE - A METABOLIC DEFECT TREATED USING A NOVEL-APPROACH TO HEPATOCELLULAR TRANSPLANTATION|
|Keywords:||INTRASPLENIC HEPATOCYTE TRANSPLANTATION, MICROCARRIER-ATTACHED HEPATOCYTES, LIVER-CELL TRANSPLANTATION, RECEPTOR-DEFICIENT RABBITS, ENZYME DEFICIENCY, GUNN-RATS, MICROENCAPSULATED HEPATOCYTES, GENE-EXPRESSION, DENDRITIC CELLS, DISEASE|
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