Biomaterial Database

Lysosome lipid storage disorder in NCTR-BALB/c mice. III. Isolation and analysis of storage inclusions from liver. 1982

C Bhuvaneswaran, and M D Morris, and H Shio, and S Fowler

Department of Biochemistry, University of Arkansas for Medical Sciences, Little Rock 72205.

Livers of NCTR-BALB/c mice, affected by excessive accumulation of cholesterol and phospholipid, were fractionated by sucrose density gradient centrifugation. Lysosomes of very low density (rho = 1.05 - 1.08) were found, which by electron microscopy appeared identical to the storage inclusions seen in fixed tissues. These lysosomes could be purified about 10-fold over the original homogenate, and represented 4% of the total protein and 30-40% of the liver acid hydrolase content. The preparations were nearly free of mitochondrial, endoplasmic reticulum, and plasma membrane contamination. The lysosomes were laden with cholesterol and phospholipid. Cholesterol (greater than 97% unesterified) accounted for half of the total lipid, and sphingomyelin accounted for another 20%. Phosphatidylcholine and phosphatidylethanolamine were also present in substantial quantities. All of the excess cholesterol and sphingomyelin of liver could be attributed to the low density lysosomes. Lysosomal acid sphingomyelinase activity, measured with a synthetic substrate, was found to be 10-60% of BALB/c mouse control levels in liver, spleen, and cerebellum, while two other lysosomal enzymes, N-acetyl-beta-glucosaminidase and beta-glucuronidase, were increased 2-8-fold in the same tissues. These data and the morphologic observations of the preceding paper establish that the disorder affecting NCTR-BALB/c mice is a lysosome storage disease. We propose several possible mechanisms to explain the cholesterol and phospholipid overloading of lysosomes. The specific gene defect remains to be established.

UI	MeSH Term	Description	Entries
D008099	Liver	A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.	Livers
D008247	Lysosomes	A class of morphologically heterogeneous cytoplasmic particles in animal and plant tissues characterized by their content of hydrolytic enzymes and the structure-linked latency of these enzymes. The intracellular functions of lysosomes depend on their lytic potential. The single unit membrane of the lysosome acts as a barrier between the enzymes enclosed in the lysosome and the external substrate. The activity of the enzymes contained in lysosomes is limited or nil unless the vesicle in which they are enclosed is ruptured or undergoes MEMBRANE FUSION. (From Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed).	Autolysosome,Autolysosomes,Lysosome
D008661	Metabolism, Inborn Errors	Errors in metabolic processes resulting from inborn genetic mutations that are inherited or acquired in utero.	Inborn Errors of Metabolism,Metabolism Errors, Inborn,Error, Inborn Metabolism,Errors Metabolism, Inborn,Errors Metabolisms, Inborn,Errors, Inborn Metabolism,Inborn Errors Metabolism,Inborn Errors Metabolisms,Inborn Metabolism Error,Inborn Metabolism Errors,Metabolism Error, Inborn,Metabolism Inborn Error,Metabolism Inborn Errors,Metabolisms, Inborn Errors
D008817	Mice, Mutant Strains	Mice bearing mutant genes which are phenotypically expressed in the animals.	Mouse, Mutant Strain,Mutant Mouse Strain,Mutant Strain of Mouse,Mutant Strains of Mice,Mice Mutant Strain,Mice Mutant Strains,Mouse Mutant Strain,Mouse Mutant Strains,Mouse Strain, Mutant,Mouse Strains, Mutant,Mutant Mouse Strains,Mutant Strain Mouse,Mutant Strains Mice,Strain Mouse, Mutant,Strain, Mutant Mouse,Strains Mice, Mutant,Strains, Mutant Mouse
D002479	Inclusion Bodies	A generic term for any circumscribed mass of foreign (e.g., lead or viruses) or metabolically inactive materials (e.g., ceroid or MALLORY BODIES), within the cytoplasm or nucleus of a cell. Inclusion bodies are in cells infected with certain filtrable viruses, observed especially in nerve, epithelial, or endothelial cells. (Stedman, 25th ed)	Cellular Inclusions,Cytoplasmic Inclusions,Bodies, Inclusion,Body, Inclusion,Cellular Inclusion,Cytoplasmic Inclusion,Inclusion Body,Inclusion, Cellular,Inclusion, Cytoplasmic,Inclusions, Cellular,Inclusions, Cytoplasmic
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D013108	Sphingomyelin Phosphodiesterase	An enzyme that catalyzes the hydrolysis of sphingomyelin to ceramide (N-acylsphingosine) plus choline phosphate. A defect in this enzyme leads to NIEMANN-PICK DISEASE. EC 3.1.4.12.	Sphingomyelin Cholinephosphohydrolase,Sphingomyelin Cleaving Enzyme,Sphingomyelinase,Sphingomyelinase C
D013347	Subcellular Fractions	Components of a cell produced by various separation techniques which, though they disrupt the delicate anatomy of a cell, preserve the structure and physiology of its functioning constituents for biochemical and ultrastructural analysis. (From Alberts et al., Molecular Biology of the Cell, 2d ed, p163)	Fraction, Subcellular,Fractions, Subcellular,Subcellular Fraction
D050356	Lipid Metabolism	Physiological processes in biosynthesis (anabolism) and degradation (catabolism) of LIPIDS.	Metabolism, Lipid
D051379	Mice	The common name for the genus Mus.	Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus