TISSUE AND CELLULAR SPECIFIC EXPRESSION OF MURINE LYSOSOMAL ACID LIPASE MESSENGER-RNA AND PROTEIN

Lysosomal acid lipase (LAL) is, essential to the intracellular control of cholesterol and triglyceride catabolism via the low density lipopr otein (LDL) delivery of these neutral lipids to the lysosome. Deficien cy of LAL in humans leads to Wolman disease and cholesteryl ester stor age disease that result, respectively, in the intralysosomal storage o f both neutral lipids or only cholesteryl esters. The mouse and human LAL cDNAs were cloned. The deduced amino acid sequences from die mouse and human LAL had high similarity (95%) and identity (75%) including conservation of the active center motifs (G-X S-X-G) and five potentia l N-glycosylation consensus sequences. Tissue specific expression of L AL mRNA and protein in mouse tissues was evaluated by in situ hybridiz ation and immunofluorescence staining, respectively. The LAL mRNA was expressed at low levels in most tissues. High level expression was fou nd in hepatocytes and splenic and thymic cells. Very high level expres sion was observed in cells of the small intestinal villi, the zona fas ciculata and reticularis of the adrenal cortex, pancreatic acini, and renal tubular epithelium. Significant levels of expression were detect ed in epithelial cells of choroid plexus in developing mouse embryo by day 12, in liver and lung by day 14, and in small intestine and kidne y by day 16. Similar distribution of LAL protein was observed by immun ofluorescence stain. Our results show that the expression of LAL is re gulated in a tissue- and cell-specific manner that corresponds to the pathologic involvement in Wolman disease.