An established light ear mutant (C57BL/6J-Pdeb(rd1) le) mouse cell line exhibits a block to secretion of lysosomal enzymes

The hypopigment mutant mice, light ear, pallid, and beige, possess defects in melanosomes, lysosomes, and platelet dense granules, suggesting that these organelles share a common biogenesis and processing. Light ear and pallid mutants are animal models for Hermansky Pudlak syndrome, whereas the beige mouse is an animal model for Chediak Higashi syndrome. An established skin cell line from the light ear mouse was tested along with pallid and beige cell lines for mutant effects on secretion of lysosomal hydrolase activities of six different lysosomal glycosidases and the trafficking of N-[5-(5,7-dimethyl BODIPY)-1-pentanoyl]-D-erythrosphingosine (C(5)-DMB-ceramide). There were no consistently significant differences between the pallid and the beige mutant cell lines or between these two mutant lines and the control cell line in the percentage secretion of lysosomal hydrolase activities. The light ear mutant cell line, however, displayed a significantly lower percentage secretion of lysosomal hydrolase activities than all other cell lines tested. The light ear mutant cells processed C(5)-DMB-ceramide completely, as seen in the control cell line, whereas pallid and beige cell lines retained fluorescent material and exhibited a block in the complete processing of C(5)-DMB-ceramide 20 h after labeling. The block to secretion of lyososomal hydrolase activities in the light ear mutant cell line will be useful for further studies on this mutant's lysosomal defect.