Morphologic and biochemical abnormalities of kidney lysosomes in mice with an inherited albinism.

The light-ear mutation in the mouse may serve as a useful model for the human inherited oculocutaneous albinisms such as the Hermansky-Pudlak and Chédiak-Higashi syndromes. The authors have investigated the kidney lysosomes of le/le mutant mice by histochemical methods. A striking increase in the staining reaction for the lysosomal enzymes beta-galactosidase and acid-phosphatase was evident in kidney cortex of the mutant mice, in comparison with +/+ controls. The lysosomal protease, cathepsin C, is also found to be elevated in the mutant. By light microscopy, there appeared to be an increase in the number of lysosomes in mutant kidney. Electron microscopy revealed the presence of large, multilamellar granules in proximal tubule cells. Analysis of sedimentation through sucrose gradients demonstrated the presence of a low-density population of lysosomes in the mutant kidney. In addition, a striking accumulation of ceroidlike pigment was observed. The molecular lesions responsible for the melanolysosomal syndromes in mice and man are still unidentified.