Increase of ornithine transcarbamylase protein in sparse-fur mice with ornithine transcarbamylase deficiency.

Ornithine transcarbamylase (OTCase, EC 2.1.3.3) a mitochondrial enzyme of the urea cycle catalyses the formation of citrulline from ornithine and carbamoyl phosphate. It has been purified from liver in 3 mammalian species: bovine [ 11, human [2] and rat [3,4] but not from mouse. We decided to purify mouse OTCase because the mouse is the only mammalian species in which two strains with an OTCase mutation have been described: sparse-fur (spf) and sparse-fur with abnormal skin and hair (spf ash) 5,6]. These two X-linked mutations are easily maintained during breeding through several generations and are good models for the study of OTCase mutations as compared to those observed in humans. We have been especially interested in mouse spf in which the OTCase activity exhibits peculiar properties: at pH 8 which is the optimum pH of the normal enzyme, the spf OTCase activity is decreased by 75% while at pH 9 it is increased by 150% as compared to control OTCase measured at its optimum pH (pH 8). The aim of our work was to answer the question raised by this observation: is this increase of OTCase activity at pH 9 only due to a physico-chemical modification of the enzyme or is it secondary to an increased amount of this protein? This latter possibility would imply that when a mutation affects the quanlitative function of an enzyme of the urea cycle, a mechanism would be triggered resulting in an increased amount of the defective protein. We describe here the purification of OTCase from mouse liver and a quantitative assay of this enzyme by an immunological procedure [7] using a specific antiserum raised in rabbit. The properties of normal and spf mouse livers are compared.