Development of a new biochemical mutation test in mice based upon measurements of enzyme activities. I. Theoretical concepts and basic procedure.

A test procedure is described for detecting germ cell mutations which alter activity of enzymes in in vivo mammalian tissues. The objective is to identify those individuals, among a population of F1 animals from treated parents, that are heterozygous for a mutation at an unspecified locus which results in an altered activity of one or more of the enzymes monitored. Animals are evaluated through three analysis screens with emphasis on identification of mutant individuals. In the first screen, activity values of a battery of enzymes are compared to their respective normal ranges to identify those which are aberrant. The mean activities and coefficients of variation useful in defining the normal ranges for 19 enzymes in C57BL/6J Nctr mice are presented along with a set of theoretical normal animal misclassification probabilities for each of these enzymes. The second screen is a Michaelis-Menten kinetic analysis of aberrant enzymes, the goal of which is to correct misclassifications of normal animals made in the first screen. A third screen of aberrant enzyme activities in a subsequent generation is used to demonstrate inheritance and confirm the mutation. The advantages and the limitations, as well as possible variations of the basic procedure are discussed.