Expression of Ornithine Transcarbamylase Deficiency in the Small Intestine and Colon of Sparse-Fur Mutant Mice

Sparse-fur mutant mice have an X-linked deficiency of liver ornithine transcarbamylase (OTC), similar to congenital hyperammonemia type II seen in children. The purpose of the present study was to see whether the expression of enzyme deficiency in the small intestine and colon was similar to that in the liver. Our results show that the level of residual OTC activity in duodenal, jejunal, and ileal mucosa is not significantly different from that of the liver, both in mutant heterozygous female and hemizygous male mice. A highly significant (p less than 0.001) positive correlation was seen between the enzyme activity from all segments of the normal and mutant intestine and that of the liver. pH dependence of mucosal OTC was similar to liver enzyme, when compared within normal or hemizygous mutant mice. Apparent Km (ornithine) of the enzyme from normal or mutant small intestine did not show any significant differences when compared with OTC from normal or mutant livers, respectively. Apparent Km (carbamyl phosphate) from both organs of normal mice was also similar. However, Km (carbamyl phosphate) of mutant intestine and liver gave variable results on statistical comparisons. The specific activity in the proximal and distal colon of mutant mice was significantly lower (p less than 0.001) than normal mice, and showed a similar expression of enzyme deficiency as seen in the small intestine. The similarity of OTC deficiency in the intestine and liver of sparse-fur mice would provide a basis for investigating the use of mucosal biopsies in the confirmation and characterization of human disease.