title: Histidinemia in mice: a metabolic defect treated using a novel approach to hepatocellular transplantation.
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.
authors.affiliation: Department of Medicine, Royal Postgraduate Medical School, London, England.
authors.forename: C
authors.initials: C
authors.lastname: Selden
authors.forename: D
authors.initials: D
authors.lastname: Calnan
authors.forename: N
authors.initials: N
authors.lastname: Morgan
authors.forename: H
authors.initials: H
authors.lastname: Wilcox
authors.forename: E
authors.initials: E
authors.lastname: Carr
authors.forename: H J
authors.initials: HJ
authors.lastname: Hodgson
mesh_terms: D000818:Animals; D017690:Cell Transplantation; D006639:Histidine / Q000097:blood* / Q000172:deficiency / Q000652:urine; D006638:Histidine Ammonia-Lyase / Q000378:metabolism; D006824:Hybridization, Genetic; D007150:Immunohistochemistry / Q000379:methods; D008099:Liver / Q000166:cytology* / Q000201:enzymology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D013194:Staining and Labeling
chemical_list: D006639:Histidine; D006638:Histidine Ammonia-Lyase