Postnatal maturation of enterocytes in sparse-fur mutant mice.
In adult sparse-fur mutant mice, ornithine transcarbamylase (OTC) activity represents only 14% of the normal values. We studied the development of this activity from birth to adult period and demonstrated that the enzyme deficiency is already fully expressed at birth, in both the liver and the small intestine of mutants. Since OTC catalyzes the conversion of ornithine to citrulline, in the presence of carbamoyl-phosphate, the effect of a disturbed ornithine metabolism on the postnatal development of the small intestine has been evaluated. The normal appearance of sucrase as well as the normal increase of glucoamylase, trehalase, and alkaline phosphatase activities are delayed in sparse-fur mice compared with controls. Moreover, normal adult values are never attained. In contrast, the normal decline of lactase activity is impaired while leucylnaphthylamidase activity is unaffected. Cell proliferation, as evaluated by [3H]thymidine incorporation into DNA and mitotic index, is less active during the 3rd wk of life in mutants. These phenomena are closely associated with a transient weak arginase and ornithine decarboxylase activity in the small intestine. Since arginase catalyzes the conversion of arginine to orthithine, thus ensuring the availability of this substrate for ornithine decarboxylase activity, these results indicate a disturbance of polyamine metabolism in mutant enterocytes with a consequent delay in postnatal differentiation and proliferation. Sparse-fur mutant mouse may therefore represent a useful animal model for evaluating the role of ornithine metabolism in the maturation process of the small intestine.
D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development*; D001119:Arginase / Q000378:metabolism; D002470:Cell Survival; D004247:DNA / Q000378:metabolism; D066298:In Vitro Techniques; D007421:Intestine, Small / Q000166:cytology* / Q000201:enzymology / Q000648:ultrastructure; D008099:Liver / Q000201:enzymology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008817:Mice, Mutant Strains / Q000254:growth & development* / Q000378:metabolism; D008871:Microvilli / Q000201:enzymology; D008940:Mitotic Index; D009954:Ornithine Carbamoyltransferase / Q000378:metabolism; D009955:Ornithine Decarboxylase / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D013936:Thymidine / Q000378:metabolism
D011506:Proteins; D004247:DNA; D009954:Ornithine Carbamoyltransferase; D001119:Arginase; D009955:Ornithine Decarboxylase; D013936:Thymidine