SIMULTANEOUS GENETIC CONTROL OF THE STRUCTURE AND RATE OF SYNTHESIS OF MURINE GLUCURONIDASE

Abstract

ABSTRACT : Inbred strains of mice can be divided into two classes based upon liver and kidney levels of β-glucuronidase. Most strains exhibit liver activity levels between 40 and 100 activity units per gram in contrast to a few strains with values between 3 and 6. Glucuronidases from high and low activity strains also exhibit a difference in structure as determined by heat sensitivity. Previous genetic studies, as well as examination of available inbred strains of mice, suggest that the genetic control of the difference in activity level as well as the difference in structure resides in the glucuronidase structural gene (Gus) . Immunochemical studies clearly show that the difference in tissue activity levels is directly related to the number of glucuronidase active sites and not to a change in the quality of the active sites. Using combined immunochemical and isotope incorporation techniques it is demonstrated that the difference in the number of active sites between high and low activity strains is a function of the rate of synthesis of glucuronidase. Several models are considered to explain structural gene control of the rate of glucuronidase synthesis, including the concept of autogenous regulation of gene expression.