Turnover of kidney beta-glucuronidase in normal and Chédiak-Higashi (beige) mice.

Kidney beta-glucuronidase turnover has been examined by specific antibody methods in normal C57BL/6J mice and in coisogenic C57BL/6J beige mice, an animal model for the human Chédiak-Higashi syndrome. No effect of the beige gene on the rate of glucuronidase synthesis was detected in either untreated or testosterone-treated mice. Moreover, glucuronidase of beige mice decayed relatively slowly in pulse labeling and in hormone withdrawal experiments. Direct measurements of secretion confirmed that both in the presence of testosterone and following its withdrawal, there was a threefold lower rate of secretion of kidney glucuronidase in beige mice. Following hormone withdrawal, the loss of glucuronidase activity in beige mice was biphasic, with the second more slowly turning over component apparently lost by a nonsecretory mechanism. This persistent nonsecreted glucuronidase activity was specifically associated with giant lysosomes in kidney proximal tubule cells near the corticomedullary border. Thus, there are two major populations of lysosomes in proximal tubule cells of beige mice. Cells of the outer cortex contain mainly morphologically normal lysosomes, and their lysosomal enzymes are secreted at near normal rates. However, lysosomal enzymes derived from the giant lysosomes of cells near the corticomedullary border are secreted either very slowly or not at all. The altered secretion of lysosomal enzymes from specific kidney cells of beige mice may serve as a model system for study of defective fusion of lysosomes with phagocytosed bacteria in cells of Chédiak-Higashi patients.