Effect of the combined lipase deficiency mutation (cld/cld) on ultrastructure of tissues in mice. Diaphragm, heart, brown adipose tissue, lung, and liver.

Lipoprotein lipase and hepatic lipase activities are very low in tissues of mice born with genetic combined lipase deficiency (cld/cld). Consequently, if allowed to suckle, the mice develop severe hyperlipemia and die within 3 days. The ultrastructure of capillaries and parenchymal cells in tissues that normally contain lipoprotein lipase and hepatic lipase was studied in tissues from cld/cld and unaffected mice 6 to 24 hours of age. Capillaries in tissues from suckled cld/cld mice were packed with numerous abnormally shaped chylomicrons. There was close contact between surfaces of chylomicrons and the luminal plasma membrane of endothelium. Chylomicrons were sometimes found between endothelial cells and in the subendothelial space in heart, lung, and liver, and in the lumen of lung alveoli. In contrast, capillaries of suckled unaffected mice contained very few chylomicrons, and the subendothelial spaces and lung alveoli were free of chylomicrons. Myocytes of diaphragm and heart from suckled cld/cld mice did not contain lipid droplets, whereas brown adipocytes contained a few small droplets. Parenchymal cells in diaphragm, heart, brown adipose tissue, and lung from suckled unaffected mice contained numerous large lipid droplets. Hepatocytes of suckled cld/cld mice contained small irregularly shaped lipoprotein particles (100 A) in endoplasmic reticulum and Golgi, numerous large lysosomes containing small lipoprotein particles, lipid spheres and lamellar structures, and no intracellular lipid droplets, whereas hepatocytes of suckled unaffected mice contained larger lipoprotein particles (400 A), large lipid droplets, and very few lysosomes. Triacylglycerol of chylomicrons from cld/cld mice was readily hydrolyzed by bovine lipoprotein lipase in vitro, and this effect was not augmented by heat-inactivated serum, indicating that the chylomicrons contained adequate amounts of apoprotein C-II. Thus, the large amount of chylomicrons in capillaries and small amount of lipid droplets in cells of suckled cld/cld mice reflect the very low level of lipoprotein lipase activity in these animals. The findings in hepatocytes indicate that lipoprotein metabolism in liver is markedly disturbed in cld/cld mice.