Abstract
We report the apparent therapeutic effects of the introduction of rat ornithine transcarb-amylase (OTC) gene composed of 1.3 kb of the 5' flanking region fused onto rat OTC cDNA into OTC-deficient spf ash mice as a fundamental approach to gene therapy. The OTC transgene caused an increase in hepatic and intestinal OTC activities of spf ash mice from 5 % to about 10 and 30 %, respectively, of controls, an increase in serum citrulline, and a decrease in urinary orotic acid, to each control level under fed conditions. The transgene was still effective under fasting conditions, but was not sufficient under nitrogen-load (oral tryptone administration at 5.6 mmol/ kg body weight) conditions, judged from urinary orotic acid excretion. Accidental tick infection caused a suppression of the OTC transgene expression which resulted in a decrease in OTC activities to those in spf-ash mice and an increase in urinary orotic acid under fasting and nitrogenload conditions. Relation between OTC activities in the liver and small intestine and urinary orotic acid under various conditions including data under conditions at tick extirmination sug-gests more important role of intestinal OTC than hepatic OTC.
