Lysosomal acid lipase (LAL) is essential to the intracellular control of cholesterol and triglyceride catabolism via the low density lipoprotein (LDL) delivery of these neutral lipids to the lysosome. Deficiency of LAL in humans leads to Wolman disease and cholesteryl ester storage disease that result, respectively, in the intralysosomal storage of both neutral lipids or only cholesteryl esters. The mouse and human LAL cDNAs were cloned. The deduced amino acid sequences from the 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 potential N-glycosylation consensus sequences. Tissue specific expression of LAL mRNA and protein in mouse tissues was evaluated by in situ hybridization and immunofluorescence staining, respectively. The LAL mRNA was expressed at low levels in most tissues. High level expression was found in hepatocytes and splenic and thymic cells. Very high level expression was observed in cells of the small intestinal villi, the zona fasciculata and reticularis of the adrenal cortex, pancreatic acini, and renal tubular epithelium. Significant levels of expression were detected 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 kidney by day 16. Similar distribution of LAL protein was observed by immunofluorescence stain. Our results show that the expression of LAL is regulated in a tissue- and cell-specific manner that corresponds to the pathologic involvement in Wolman disease.-Du, H., D. P. Witte, and G. A. Grabowski. Tissue and cellular specific expression of murine lysosomal acid lipase mRNA and protein.