DECREASED HYPERAMMONEMIA AND OROTIC ACIDURIA DUE TO INACTIVATION OF ORNITHINE AMINOTRANSFERASE IN MICE WITH A HEREDITARY ABNORMAL ORNITHINECARBAMOYLTRANSFERASE

Mice with the X-chromosomal sparse-fur (spf) mutation are an animal mo del of some hereditary deficiencies of ornithine carbamoyltransferase (OCT) in man. Orotic aciduria and hyperammonaemia are the most conspic uous metabolic changes in these diseases. Selective inactivation of or nithine aminotransferase (OAT) by 5-fluoromethylornithine raises endog enous ornithine concentrations so that citrulline formation is effecti vely catalysed by the aberrant OCT, in spite of its low affinity for o rnithine. As a consequence, blood and tissue ammonia concentrations an d erotic acid excretion are reduced near to normal values, and the abn ormal amino acid patterns in blood, brain and liver are normalized. Se lective inactivation of OAT seems a promising therapeutic approach in some hereditary OCT deficiencies, and a tool that may allow us to clar ify the role of ammonia and erotic acid in the development of nanism a nd abnormal behaviour in spf mutant mice.