Lysosomal Storage Diseases: Inborn errors of metabolism characterized by defects in specific lysosomal hydrolases and resulting in intracellular accumulation of unmetabolized substrates.Lysosomal Storage Diseases, Nervous System: A group of enzymatic disorders affecting the nervous system and to a variable degree the skeletal system, lymphoreticular system, and other organs. The conditions are marked by an abnormal accumulation of catabolic material within lysosomes.alpha-Mannosidosis: An inborn error of metabolism marked by a defect in the lysosomal isoform of ALPHA-MANNOSIDASE activity that results in lysosomal accumulation of mannose-rich intermediate metabolites. Virtually all patients have psychomotor retardation, facial coarsening, and some degree of dysostosis multiplex. It is thought to be an autosomal recessive disorder.Mucopolysaccharidosis VII: Mucopolysaccharidosis characterized by excessive dermatan and heparan sulfates in the urine and Hurler-like features. It is caused by a deficiency of beta-glucuronidase.Glycogen Storage Disease Type I: An autosomal recessive disease in which gene expression of glucose-6-phosphatase is absent, resulting in hypoglycemia due to lack of glucose production. Accumulation of glycogen in liver and kidney leads to organomegaly, particularly massive hepatomegaly. Increased concentrations of lactic acid and hyperlipidemia appear in the plasma. Clinical gout often appears in early childhood.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. Such rupture is supposed to be under metabolic (hormonal) control. (From Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed)Gaucher Disease: An autosomal recessive disorder caused by a deficiency of acid beta-glucosidase (GLUCOSYLCERAMIDASE) leading to intralysosomal accumulation of glycosylceramide mainly in cells of the MONONUCLEAR PHAGOCYTE SYSTEM. The characteristic Gaucher cells, glycosphingolipid-filled HISTIOCYTES, displace normal cells in BONE MARROW and visceral organs causing skeletal deterioration, hepatosplenomegaly, and organ dysfunction. There are several subtypes based on the presence and severity of neurological involvement.Fucosidosis: An autosomal recessive lysosomal storage disease caused by a deficiency of ALPHA-L-FUCOSIDASE activity resulting in an accumulation of fucose containing SPHINGOLIPIDS; GLYCOPROTEINS, and mucopolysaccharides (GLYCOSAMINOGLYCANS) in lysosomes. The infantile form (type I) features psychomotor deterioration, MUSCLE SPASTICITY, coarse facial features, growth retardation, skeletal abnormalities, visceromegaly, SEIZURES, recurrent infections, and MACROGLOSSIA, with death occurring in the first decade of life. Juvenile fucosidosis (type II) is the more common variant and features a slowly progressive decline in neurologic function and angiokeratoma corporis diffusum. Type II survival may be through the fourth decade of life. (From Menkes, Textbook of Child Neurology, 5th ed, p87; Am J Med Genet 1991 Jan;38(1):111-31)Glycogen Storage Disease: A group of inherited metabolic disorders involving the enzymes responsible for the synthesis and degradation of glycogen. In some patients, prominent liver involvement is presented. In others, more generalized storage of glycogen occurs, sometimes with prominent cardiac involvement.Mucopolysaccharidosis I: Systemic lysosomal storage disease caused by a deficiency of alpha-L-iduronidase (IDURONIDASE) and characterized by progressive physical deterioration with urinary excretion of DERMATAN SULFATE and HEPARAN SULFATE. There are three recognized phenotypes representing a spectrum of clinical severity from severe to mild: Hurler syndrome, Hurler-Scheie syndrome and Scheie syndrome (formerly mucopolysaccharidosis V). Symptoms may include DWARFISM; hepatosplenomegaly; thick, coarse facial features with low nasal bridge; corneal clouding; cardiac complications; and noisy breathing.Glycogen Storage Disease Type II: An autosomal recessively inherited glycogen storage disease caused by GLUCAN 1,4-ALPHA-GLUCOSIDASE deficiency. Large amounts of GLYCOGEN accumulate in the LYSOSOMES of skeletal muscle (MUSCLE, SKELETAL); HEART; LIVER; SPINAL CORD; and BRAIN. Three forms have been described: infantile, childhood, and adult. The infantile form is fatal in infancy and presents with hypotonia and a hypertrophic cardiomyopathy (CARDIOMYOPATHY, HYPERTROPHIC). The childhood form usually presents in the second year of life with proximal weakness and respiratory symptoms. The adult form consists of a slowly progressive proximal myopathy. (From Muscle Nerve 1995;3:S61-9; Menkes, Textbook of Child Neurology, 5th ed, pp73-4)Aspartylglucosaminuria: A recessively inherited, progressive lysosomal storage disease caused by a deficiency of GLYCOSYLASPARAGINASE activity. The lack of this enzyme activity results in the accumulation of N-acetylglucosaminylasparagine (the linkage unit of asparagine-linked glycoproteins) in LYSOSOMES.Mucolipidoses: A group of inherited metabolic diseases characterized by the accumulation of excessive amounts of acid mucopolysaccharides, sphingolipids, and/or glycolipids in visceral and mesenchymal cells. Abnormal amounts of sphingolipids or glycolipids are present in neural tissue. INTELLECTUAL DISABILITY and skeletal changes, most notably dysostosis multiplex, occur frequently. (From Joynt, Clinical Neurology, 1992, Ch56, pp36-7)Enzyme Replacement Therapy: Therapeutic replacement or supplementation of defective or missing enzymes to alleviate the effects of enzyme deficiency (e.g., GLUCOSYLCERAMIDASE replacement for GAUCHER DISEASE).Sphingolipidoses: A group of inherited metabolic disorders characterized by the intralysosomal accumulation of SPHINGOLIPIDS primarily in the CENTRAL NERVOUS SYSTEM and to a variable degree in the visceral organs. They are classified by the enzyme defect in the degradation pathway and the substrate accumulation (or storage). Clinical features vary in subtypes but neurodegeneration is a common sign.Leukodystrophy, Metachromatic: An autosomal recessive metabolic disease caused by a deficiency of CEREBROSIDE-SULFATASE leading to intralysosomal accumulation of cerebroside sulfate (SULFOGLYCOSPHINGOLIPIDS) in the nervous system and other organs. Pathological features include diffuse demyelination, and metachromatically-staining granules in many cell types such as the GLIAL CELLS. There are several allelic and nonallelic forms with a variety of neurological symptoms.Mucopolysaccharidosis III: Mucopolysaccharidosis characterized by heparitin sulfate in the urine, progressive mental retardation, mild dwarfism, and other skeletal disorders. There are four clinically indistinguishable but biochemically distinct forms, each due to a deficiency of a different enzyme.Aspartylglucosylaminase: An enzyme that catalyzes the conversion of N(4)-(beta-N-acetyl-D-glucosaminyl)-L-asparagine and water to N-acetyl-beta-D-glucosaminylamine and L-aspartate. It acts only on asparagine-oligosaccharides containing one amino acid, i.e. the ASPARAGINE has free alpha-amino and alpha-carboxyl groups. (From Enzyme Nomenclature, 1992)Cerebroside-Sulfatase: An enzyme that catalyzes the hydrolysis of cerebroside 3-sulfate (sulfatide) to yield a cerebroside and inorganic sulfate. A marked deficiency of arylsulfatase A, which is considered the heat-labile component of cerebroside sulfatase, has been demonstrated in all forms of metachromatic leukodystrophy (LEUKODYSTROPHY, METACHROMATIC). EC 3.1.6.8.Iduronidase: An enzyme that hydrolyzes iduronosidic linkages in desulfated dermatan. Deficiency of this enzyme produces Hurler's syndrome. EC 3.2.1.76.Sandhoff Disease: An autosomal recessive neurodegenerative disorder characterized by an accumulation of G(M2) GANGLIOSIDE in neurons and other tissues. It is caused by mutation in the common beta subunit of HEXOSAMINIDASE A and HEXOSAMINIDASE B. Thus this disease is also known as the O variant since both hexosaminidase A and B are missing. Clinically, it is indistinguishable from TAY-SACHS DISEASE.Gangliosidosis, GM1: An autosomal recessive neurodegenerative disorder caused by the absence or deficiency of BETA-GALACTOSIDASE. It is characterized by intralysosomal accumulation of G(M1) GANGLIOSIDE and oligosaccharides, primarily in neurons of the central nervous system. The infantile form is characterized by MUSCLE HYPOTONIA, poor psychomotor development, HIRSUTISM, hepatosplenomegaly, and facial abnormalities. The juvenile form features HYPERACUSIS; SEIZURES; and psychomotor retardation. The adult form features progressive DEMENTIA; ATAXIA; and MUSCLE SPASTICITY. (From Menkes, Textbook of Child Neurology, 5th ed, pp96-7)Cholesterol Ester Storage Disease: An autosomal recessive disorder caused by mutations in the gene for acid lipase (STEROL ESTERASE). It is characterized by the accumulation of neutral lipids, particularly CHOLESTEROL ESTERS in leukocytes, fibroblasts, and hepatocytes.Gangliosidoses, GM2: A group of recessively inherited diseases characterized by the intralysosomal accumulation of G(M2) GANGLIOSIDE in the neuronal cells. Subtypes include mutations of enzymes in the BETA-N-ACETYLHEXOSAMINIDASES system or G(M2) ACTIVATOR PROTEIN leading to disruption of normal degradation of GANGLIOSIDES, a subclass of ACIDIC GLYCOSPHINGOLIPIDS.Glucosylceramidase: A glycosidase that hydrolyzes a glucosylceramide to yield free ceramide plus glucose. Deficiency of this enzyme leads to abnormally high concentrations of glucosylceramide in the brain in GAUCHER DISEASE. EC 3.2.1.45.Mucopolysaccharidosis VI: Mucopolysaccharidosis with excessive CHONDROITIN SULFATE B in urine, characterized by dwarfism and deafness. It is caused by a deficiency of N-ACETYLGALACTOSAMINE-4-SULFATASE (arylsulfatase B).alpha-Galactosidase: An enzyme that catalyzes the hydrolysis of terminal, non-reducing alpha-D-galactose residues in alpha-galactosides including galactose oligosaccharides, galactomannans, and galactolipids.Neuronal Ceroid-Lipofuscinoses: A group of severe neurodegenerative diseases characterized by intracellular accumulation of autofluorescent wax-like lipid materials (CEROID; LIPOFUSCIN) in neurons. There are several subtypes based on mutations of the various genes, time of disease onset, and severity of the neurological defects such as progressive DEMENTIA; SEIZURES; and visual failure.Metabolism, Inborn Errors: Errors in metabolic processes resulting from inborn genetic mutations that are inherited or acquired in utero.Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges.Glycogen Storage Disease Type IV: An autosomal recessive metabolic disorder due to a deficiency in expression of glycogen branching enzyme 1 (alpha-1,4-glucan-6-alpha-glucosyltransferase), resulting in an accumulation of abnormal GLYCOGEN with long outer branches. Clinical features are MUSCLE HYPOTONIA and CIRRHOSIS. Death from liver disease usually occurs before age 2.Glycogen Storage Disease Type III: An autosomal recessive metabolic disorder due to deficient expression of amylo-1,6-glucosidase (one part of the glycogen debranching enzyme system). The clinical course of the disease is similar to that of glycogen storage disease type I, but milder. Massive hepatomegaly, which is present in young children, diminishes and occasionally disappears with age. Levels of glycogen with short outer branches are elevated in muscle, liver, and erythrocytes. Six subgroups have been identified, with subgroups Type IIIa and Type IIIb being the most prevalent.Mucopolysaccharidoses: Group of lysosomal storage diseases each caused by an inherited deficiency of an enzyme involved in the degradation of glycosaminoglycans (mucopolysaccharides). The diseases are progressive and often display a wide spectrum of clinical severity within one enzyme deficiency.Fabry Disease: An X-linked inherited metabolic disease caused by a deficiency of lysosomal ALPHA-GALACTOSIDASE A. It is characterized by intralysosomal accumulation of globotriaosylceramide and other GLYCOSPHINGOLIPIDS in blood vessels throughout the body leading to multi-system complications including renal, cardiac, cerebrovascular, and skin disorders.alpha-Glucosidases: Enzymes that catalyze the exohydrolysis of 1,4-alpha-glucosidic linkages with release of alpha-glucose. Deficiency of alpha-1,4-glucosidase may cause GLYCOGEN STORAGE DISEASE TYPE II.GlucuronidaseN-Acetylgalactosamine-4-Sulfatase: An arylsulfatase that catalyzes the hydrolysis of the 4-sulfate groups of the N-acetyl-D-galactosamine 4-sulfate units of chondroitin sulfate and dermatan sulfate. A deficiency of this enzyme is responsible for the inherited lysosomal disease, Maroteaux-Lamy syndrome (MUCOPOLYSACCHARIDOSIS VI). EC 3.1.6.12.Niemann-Pick Diseases: A group of autosomal recessive disorders in which harmful quantities of lipids accumulate in the viscera and the central nervous system. They can be caused by deficiencies of enzyme activities (SPHINGOMYELIN PHOSPHODIESTERASE) or defects in intracellular transport, resulting in the accumulation of SPHINGOMYELINS and CHOLESTEROL. There are various subtypes based on their clinical and genetic differences.Mucopolysaccharidosis IV: Genetic disorder of mucopolysaccharide metabolism characterized by skeletal abnormalities, joint instability, development of cervical myelopathy, and excessive urinary keratan sulfate. There are two biochemically distinct forms, each due to a deficiency of a different enzyme.beta-N-Acetylhexosaminidases: A hexosaminidase specific for non-reducing N-acetyl-D-hexosamine residues in N-acetyl-beta-D-hexosaminides. It acts on GLUCOSIDES; GALACTOSIDES; and several OLIGOSACCHARIDES. Two specific mammalian isoenzymes of beta-N-acetylhexoaminidase are referred to as HEXOSAMINIDASE A and HEXOSAMINIDASE B. Deficiency of the type A isoenzyme causes TAY-SACHS DISEASE, while deficiency of both A and B isozymes causes SANDHOFF DISEASE. The enzyme has also been used as a tumor marker to distinguish between malignant and benign disease.beta-Mannosidosis: An inborn error of metabolism marked by a defect in the lysosomal isoform of BETA-MANNOSIDASE that results in lysosomal accumulation of mannose-rich intermediate metabolites containing 1,4-beta linkages. The human disease occurs through autosomal recessive inheritance and manifests itself with variety of symptoms that depend upon the type of gene mutation.Plant Poisoning: Poisoning by the ingestion of plants or its leaves, berries, roots or stalks. The manifestations in both humans and animals vary in severity from mild to life threatening. In animals, especially domestic animals, it is usually the result of ingesting moldy or fermented forage.Tay-Sachs Disease: An autosomal recessive neurodegenerative disorder characterized by the onset in infancy of an exaggerated startle response, followed by paralysis, dementia, and blindness. It is caused by mutation in the alpha subunit of the HEXOSAMINIDASE A resulting in lipid-laden ganglion cells. It is also known as the B variant (with increased HEXOSAMINIDASE B but absence of hexosaminidase A) and is strongly associated with Ashkenazic Jewish ancestry.Hexosaminidase B: A mammalian beta-hexosaminidase isoform that is comprized of hexosaminidase beta subunits. Deficiency of hexosaminidase B due to mutations in the gene encoding the hexosaminidase beta subunit is a case of SANDHOFF DISEASE.Malvaceae: The mallow family of the order Malvales, subclass Dilleniidae, class Magnoliopsida. Members include GOSSYPIUM, okra (ABELMOSCHUS), HIBISCUS, and CACAO. The common names of hollyhock and mallow are used for several genera of Malvaceae.Wolman Disease: The severe infantile form of inherited lysosomal lipid storage diseases due to deficiency of acid lipase (STEROL ESTERASE). It is characterized by the accumulation of neutral lipids, particularly CHOLESTEROL ESTERS in leukocytes, fibroblasts, and hepatocytes. It is also known as Wolman's xanthomatosis and is an allelic variant of CHOLESTEROL ESTER STORAGE DISEASE.Genetic Therapy: Techniques and strategies which include the use of coding sequences and other conventional or radical means to transform or modify cells for the purpose of treating or reversing disease conditions.G(M2) Ganglioside: A glycosphingolipid that accumulates due to a deficiency of hexosaminidase A or B (BETA-N-ACETYLHEXOSAMINIDASES), or GM2 activator protein, resulting in GANGLIOSIDOSES, heredity metabolic disorders that include TAY-SACHS DISEASE and SANDHOFF DISEASE.alpha-Mannosidase: An enzyme that catalyzes the HYDROLYSIS of terminal, non-reducing alpha-D-mannose residues in alpha-D-mannosides. The enzyme plays a role in the processing of newly formed N-glycans and in degradation of mature GLYCOPROTEINS. There are multiple isoforms of alpha-mannosidase, each having its own specific cellular location and pH optimum. Defects in the lysosomal form of the enzyme results in a buildup of mannoside intermediate metabolites and the disease ALPHA-MANNOSIDOSIS.Leukodystrophy, Globoid Cell: An autosomal recessive metabolic disorder caused by a deficiency of GALACTOSYLCERAMIDASE leading to intralysosomal accumulation of galactolipids such as GALACTOSYLCERAMIDES and PSYCHOSINE. It is characterized by demyelination associated with large multinucleated globoid cells, predominantly involving the white matter of the central nervous system. The loss of MYELIN disrupts normal conduction of nerve impulses.Gangliosidoses: A group of autosomal recessive lysosomal storage disorders marked by the accumulation of GANGLIOSIDES. They are caused by impaired enzymes or defective cofactors required for normal ganglioside degradation in the LYSOSOMES. Gangliosidoses are classified by the specific ganglioside accumulated in the defective degradation pathway.Sialic Acid Storage Disease: Autosomal recessive neurodegenerative disorders caused by lysosomal membrane transport defects that result in accumulation of free sialic acid (N-ACETYLNEURAMINIC ACID) within the lysosomes. The two main clinical phenotypes, which are allelic variants of the SLC17A5 gene, are ISSD, a severe infantile form, or Salla disease, a slowly progressive adult form, named for the geographic area in Finland where the kindred first studied resided.Serine Proteases: Peptide hydrolases that contain at the active site a SERINE residue involved in catalysis.beta-Glucosidase: An exocellulase with specificity for a variety of beta-D-glycoside substrates. It catalyzes the hydrolysis of terminal non-reducing residues in beta-D-glucosides with release of GLUCOSE.Chondro-4-Sulfatase: An enzyme from the sulfuric ester hydrolase class that breaks down one of the products of the chondroitin lyase II reaction. EC 3.1.6.9.Disease Models, Animal: Naturally occurring or experimentally induced animal diseases with pathological processes sufficiently similar to those of human diseases. They are used as study models for human diseases.Dependovirus: A genus of the family PARVOVIRIDAE, subfamily PARVOVIRINAE, which are dependent on a coinfection with helper adenoviruses or herpesviruses for their efficient replication. The type species is Adeno-associated virus 2.Brain: The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM.Nervous System: The entire nerve apparatus, composed of a central part, the brain and spinal cord, and a peripheral part, the cranial and spinal nerves, autonomic ganglia, and plexuses. (Stedman, 26th ed)Cystinosis: A metabolic disease characterized by the defective transport of CYSTINE across the lysosomal membrane due to mutation of a membrane protein cystinosin. This results in cystine accumulation and crystallization in the cells causing widespread tissue damage. In the KIDNEY, nephropathic cystinosis is a common cause of RENAL FANCONI SYNDROME.Glycogen Storage Disease Type VII: An autosomal recessive glycogen storage disease in which there is deficient expression of 6-phosphofructose 1-kinase in muscle (PHOSPHOFRUCTOKINASE-1, MUSCLE TYPE) resulting in abnormal deposition of glycogen in muscle tissue. These patients have severe congenital muscular dystrophy and are exercise intolerant.Psychosine: An intermediate in the biosynthesis of cerebrosides. It is formed by reaction of sphingosine with UDP-galactose and then itself reacts with fatty acid-Coenzyme A to form the cerebroside.Hexosaminidase A: A mammalian beta-hexosaminidase isoform that is a heteromeric protein comprized of both hexosaminidase alpha and hexosaminidase beta subunits. Deficiency of hexosaminidase A due to mutations in the gene encoding the hexosaminidase alpha subunit is a case of TAY-SACHS DISEASE. Deficiency of hexosaminidase A and HEXOSAMINIDASE B due to mutations in the gene encoding the hexosaminidase beta subunit is a case of SANDHOFF DISEASE.Mannosephosphates: Phosphoric acid esters of mannose.Genetic Vectors: DNA molecules capable of autonomous replication within a host cell and into which other DNA sequences can be inserted and thus amplified. Many are derived from PLASMIDS; BACTERIOPHAGES; or VIRUSES. They are used for transporting foreign genes into recipient cells. Genetic vectors possess a functional replicator site and contain GENETIC MARKERS to facilitate their selective recognition.Glucosylceramides: Cerebrosides which contain as their polar head group a glucose moiety bound in glycosidic linkage to the hydroxyl group of ceramides. Their accumulation in tissue, due to a defect in beta-glucosidase, is the cause of Gaucher's disease.Glycosaminoglycans: Heteropolysaccharides which contain an N-acetylated hexosamine in a characteristic repeating disaccharide unit. The repeating structure of each disaccharide involves alternate 1,4- and 1,3-linkages consisting of either N-acetylglucosamine or N-acetylgalactosamine.Multiple Sulfatase Deficiency Disease: An inherited metabolic disorder characterized by the intralysosomal accumulation of sulfur-containing lipids (sulfatides) and MUCOPOLYSACCHARIDES. Excess levels of both substrates are present in urine. This is a disorder of multiple sulfatase (arylsulfatases A, B, and C) deficiency which is caused by the mutation of sulfatase-modifying factor-1. Neurological deterioration is rapid.Niemann-Pick Disease, Type C: An autosomal recessive lipid storage disorder that is characterized by accumulation of CHOLESTEROL and SPHINGOMYELINS in cells of the VISCERA and the CENTRAL NERVOUS SYSTEM. Type C (or C1) and type D are allelic disorders caused by mutation of gene (NPC1) encoding a protein that mediate intracellular cholesterol transport from lysosomes. Clinical signs include hepatosplenomegaly and chronic neurological symptoms. Type D is a variant in people with a Nova Scotia ancestry.Transient Receptor Potential Channels: A broad group of eukaryotic six-transmembrane cation channels that are classified by sequence homology because their functional involvement with SENSATION is varied. They have only weak voltage sensitivity and ion selectivity. They are named after a DROSOPHILA mutant that displayed transient receptor potentials in response to light. A 25-amino-acid motif containing a TRP box (EWKFAR) just C-terminal to S6 is found in TRPC, TRPV and TRPM subgroups. ANKYRIN repeats are found in TRPC, TRPV & TRPN subgroups. Some are functionally associated with TYROSINE KINASE or TYPE C PHOSPHOLIPASES.Liver: A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.Mucopolysaccharidosis II: Systemic lysosomal storage disease marked by progressive physical deterioration and caused by a deficiency of L-sulfoiduronate sulfatase. This disease differs from MUCOPOLYSACCHARIDOSIS I by slower progression, lack of corneal clouding, and X-linked rather than autosomal recessive inheritance. The mild form produces near-normal intelligence and life span. The severe form usually causes death by age 15.Mutation: Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.Mice, Knockout: Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.Mannosidases: Glycoside hydrolases that catalyze the hydrolysis of alpha or beta linked MANNOSE.Dipeptidyl-Peptidases and Tripeptidyl-Peptidases: A subclass of exopeptidases that includes enzymes which cleave either two or three AMINO ACIDS from the end of a peptide chain.Glycosphingolipids: Lipids containing at least one monosaccharide residue and either a sphingoid or a ceramide (CERAMIDES). They are subdivided into NEUTRAL GLYCOSPHINGOLIPIDS comprising monoglycosyl- and oligoglycosylsphingoids and monoglycosyl- and oligoglycosylceramides; and ACIDIC GLYCOSPHINGOLIPIDS which comprises sialosylglycosylsphingolipids (GANGLIOSIDES); SULFOGLYCOSPHINGOLIPIDS (formerly known as sulfatides), glycuronoglycosphingolipids, and phospho- and phosphonoglycosphingolipids. (From IUPAC's webpage)Glucose-6-Phosphatase: An enzyme that catalyzes the conversion of D-glucose 6-phosphate and water to D-glucose and orthophosphate. EC 3.1.3.9.Central Nervous System Diseases: Diseases of any component of the brain (including the cerebral hemispheres, diencephalon, brain stem, and cerebellum) or the spinal cord.Phenotype: The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.TRPM Cation Channels: A subgroup of TRP cation channels named after melastatin protein. They have the TRP domain but lack ANKYRIN repeats. Enzyme domains in the C-terminus leads to them being called chanzymes.Molecular Sequence Data: Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.Mice, Mutant Strains: Mice bearing mutant genes which are phenotypically expressed in the animals.Autophagy: The segregation and degradation of damaged or unwanted cytoplasmic constituents by autophagic vacuoles (cytolysosomes) composed of LYSOSOMES containing cellular components in the process of digestion; it plays an important role in BIOLOGICAL METAMORPHOSIS of amphibians, in the removal of bone by osteoclasts, and in the degradation of normal cell components in nutritional deficiency states.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.Acetylglucosaminidase: A beta-N-Acetylhexosaminidase that catalyzes the hydrolysis of terminal, non-reducing 2-acetamido-2-deoxy-beta-glucose residues in chitobiose and higher analogs as well as in glycoproteins. Has been used widely in structural studies on bacterial cell walls and in the study of diseases such as MUCOLIPIDOSIS and various inflammatory disorders of muscle and connective tissue.Cat Diseases: Diseases of the domestic cat (Felis catus or F. domesticus). This term does not include diseases of the so-called big cats such as CHEETAHS; LIONS; tigers, cougars, panthers, leopards, and other Felidae for which the heading CARNIVORA is used.Glycogen Storage Disease Type V: Glycogenosis due to muscle phosphorylase deficiency. Characterized by painful cramps following sustained exercise.Lipid Metabolism, Inborn Errors: Errors in the metabolism of LIPIDS resulting from inborn genetic MUTATIONS that are heritable.Carbohydrate Metabolism, Inborn ErrorsGlycogen Debranching Enzyme System: 1,4-alpha-D-Glucan-1,4-alpha-D-glucan 4-alpha-D-glucosyltransferase/dextrin 6 alpha-D-glucanohydrolase. An enzyme system having both 4-alpha-glucanotransferase (EC 2.4.1.25) and amylo-1,6-glucosidase (EC 3.2.1.33) activities. As a transferase it transfers a segment of a 1,4-alpha-D-glucan to a new 4-position in an acceptor, which may be glucose or another 1,4-alpha-D-glucan. As a glucosidase it catalyzes the endohydrolysis of 1,6-alpha-D-glucoside linkages at points of branching in chains of 1,4-linked alpha-D-glucose residues. Amylo-1,6-glucosidase activity is deficient in glycogen storage disease type III.Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.Hydrolases: Any member of the class of enzymes that catalyze the cleavage of the substrate and the addition of water to the resulting molecules, e.g., ESTERASES, glycosidases (GLYCOSIDE HYDROLASES), lipases, NUCLEOTIDASES, peptidases (PEPTIDE HYDROLASES), and phosphatases (PHOSPHORIC MONOESTER HYDROLASES). EC 3.Glycogen Storage Disease Type VI: A hepatic GLYCOGEN STORAGE DISEASE in which there is an apparent deficiency of hepatic phosphorylase (GLYCOGEN PHOSPHORYLASE, LIVER FORM) activity.Drug Storage: The process of keeping pharmaceutical products in an appropriate location.Iduronate Sulfatase: An enzyme that specifically cleaves the ester sulfate of iduronic acid. Its deficiency has been demonstrated in Hunter's syndrome, which is characterized by an excess of dermatan sulfate and heparan sulfate. EC 3.1.6.13.1-Deoxynojirimycin: An alpha-glucosidase inhibitor with antiviral action. Derivatives of deoxynojirimycin may have anti-HIV activity.Mice, Inbred C57BLPeripheral Nervous System: The nervous system outside of the brain and spinal cord. The peripheral nervous system has autonomic and somatic divisions. The autonomic nervous system includes the enteric, parasympathetic, and sympathetic subdivisions. The somatic nervous system includes the cranial and spinal nerves and their ganglia and the peripheral sensory receptors.Lipidoses: Conditions characterized by abnormal lipid deposition due to disturbance in lipid metabolism, such as hereditary diseases involving lysosomal enzymes required for lipid breakdown. They are classified either by the enzyme defect or by the type of lipid involved.Gene Transfer Techniques: The introduction of functional (usually cloned) GENES into cells. A variety of techniques and naturally occurring processes are used for the gene transfer such as cell hybridization, LIPOSOMES or microcell-mediated gene transfer, ELECTROPORATION, chromosome-mediated gene transfer, TRANSFECTION, and GENETIC TRANSDUCTION. Gene transfer may result in genetically transformed cells and individual organisms.Imino Sugars: Sugars in which the OXYGEN is replaced by a NITROGEN atom. This substitution prevents normal METABOLISM resulting in inhibition of GLYCOSIDASES and GLYCOSYLTRANSFERASES.Cells, Cultured: Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.beta-Mannosidase: An enzyme that catalyzes the hydrolysis of terminal, non-reducing beta-D-mannose residues in beta-D-mannosides. The enzyme plays a role in the lysosomal degradation of the N-glycosylprotein glycans. Defects in the lysosomal form of the enzyme in humans result in a buildup of mannoside intermediate metabolites and the disease BETA-MANNOSIDOSIS.beta-Galactosidase: A group of enzymes that catalyzes the hydrolysis of terminal, non-reducing beta-D-galactose residues in beta-galactosides. Deficiency of beta-Galactosidase A1 may cause GANGLIOSIDOSIS, GM1.Cats: The domestic cat, Felis catus, of the carnivore family FELIDAE, comprising over 30 different breeds. The domestic cat is descended primarily from the wild cat of Africa and extreme southwestern Asia. Though probably present in towns in Palestine as long ago as 7000 years, actual domestication occurred in Egypt about 4000 years ago. (From Walker's Mammals of the World, 6th ed, p801)Microscopy, Electron: Microscopy using an electron beam, instead of light, to visualize the sample, thereby allowing much greater magnification. The interactions of ELECTRONS with specimens are used to provide information about the fine structure of that specimen. In TRANSMISSION ELECTRON MICROSCOPY the reactions of the electrons that are transmitted through the specimen are imaged. In SCANNING ELECTRON MICROSCOPY an electron beam falls at a non-normal angle on the specimen and the image is derived from the reactions occurring above the plane of the specimen.Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Hepatomegaly: Enlargement of the liver.Spleen: An encapsulated lymphatic organ through which venous blood filters.Dogs: The domestic dog, Canis familiaris, comprising about 400 breeds, of the carnivore family CANIDAE. They are worldwide in distribution and live in association with people. (Walker's Mammals of the World, 5th ed, p1065)GlycogenOligosaccharides: Carbohydrates consisting of between two (DISACCHARIDES) and ten MONOSACCHARIDES connected by either an alpha- or beta-glycosidic link. They are found throughout nature in both the free and bound form.Enteric Nervous System: Two ganglionated neural plexuses in the gut wall which form one of the three major divisions of the autonomic nervous system. The enteric nervous system innervates the gastrointestinal tract, the pancreas, and the gallbladder. It contains sensory neurons, interneurons, and motor neurons. Thus the circuitry can autonomously sense the tension and the chemical environment in the gut and regulate blood vessel tone, motility, secretions, and fluid transport. The system is itself governed by the central nervous system and receives both parasympathetic and sympathetic innervation. (From Kandel, Schwartz, and Jessel, Principles of Neural Science, 3d ed, p766)Central Nervous System Neoplasms: Benign and malignant neoplastic processes that arise from or secondarily involve the brain, spinal cord, or meninges.alpha-N-Acetylgalactosaminidase: A hexosaminidase with specificity for terminal non-reducing N-acetyl-D-galactosamine residues in N-acetyl-alpha-D-galactosaminides.Recombinant Proteins: Proteins prepared by recombinant DNA technology.Cathepsin A: A carboxypeptidase that catalyzes the release of a C-terminal amino acid with a broad specificity. It also plays a role in the LYSOSOMES by protecting BETA-GALACTOSIDASE and NEURAMINIDASE from degradation. It was formerly classified as EC 3.4.12.1 and EC 3.4.21.13.Glycogen Storage Disease Type VIII: An x-linked recessive hepatic glycogen storage disease resulting from lack of expression of phosphorylase-b-kinase activity. Symptoms are relatively mild; hepatomegaly, increased liver glycogen, and decreased leukocyte phosphorylase are present. Liver shrinkage occurs in response to glucagon.Glucan 1,4-alpha-Glucosidase: An enzyme that catalyzes the hydrolysis of terminal 1,4-linked alpha-D-glucose residues successively from non-reducing ends of polysaccharide chains with the release of beta-glucose. It is also able to hydrolyze 1,6-alpha-glucosidic bonds when the next bond in sequence is 1,4.Niemann-Pick Disease, Type A: The classic infantile form of Niemann-Pick Disease, caused by mutation in SPHINGOMYELIN PHOSPHODIESTERASE. It is characterized by accumulation of SPHINGOMYELINS in the cells of the MONONUCLEAR PHAGOCYTE SYSTEM and other cell throughout the body leading to cell death. Clinical signs include JAUNDICE, hepatosplenomegaly, and severe brain damage.Protein Transport: The process of moving proteins from one cellular compartment (including extracellular) to another by various sorting and transport mechanisms such as gated transport, protein translocation, and vesicular transport.Polymerase Chain Reaction: In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships.Proteins: Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Food Storage: Keeping food for later consumption.Nervous System Diseases: Diseases of the central and peripheral nervous system. This includes disorders of the brain, spinal cord, cranial nerves, peripheral nerves, nerve roots, autonomic nervous system, neuromuscular junction, and muscle.Autonomic Nervous System: The ENTERIC NERVOUS SYSTEM; PARASYMPATHETIC NERVOUS SYSTEM; and SYMPATHETIC NERVOUS SYSTEM taken together. Generally speaking, the autonomic nervous system regulates the internal environment during both peaceful activity and physical or emotional stress. Autonomic activity is controlled and integrated by the CENTRAL NERVOUS SYSTEM, especially the HYPOTHALAMUS and the SOLITARY NUCLEUS, which receive information relayed from VISCERAL AFFERENTS.SulfatasesSaposins: A group of four homologous sphingolipid activator proteins that are formed from proteolytic cleavage of a common protein precursor molecule referred to as prosaposin.Bone Marrow Transplantation: The transference of BONE MARROW from one human or animal to another for a variety of purposes including HEMATOPOIETIC STEM CELL TRANSPLANTATION or MESENCHYMAL STEM CELL TRANSPLANTATION.Antiporters: Membrane transporters that co-transport two or more dissimilar molecules in the opposite direction across a membrane. Usually the transport of one ion or molecule is against its electrochemical gradient and is "powered" by the movement of another ion or molecule with its electrochemical gradient.Sympathetic Nervous System: The thoracolumbar division of the autonomic nervous system. Sympathetic preganglionic fibers originate in neurons of the intermediolateral column of the spinal cord and project to the paravertebral and prevertebral ganglia, which in turn project to target organs. The sympathetic nervous system mediates the body's response to stressful situations, i.e., the fight or flight reactions. It often acts reciprocally to the parasympathetic system.Galactosylceramidase: An enzyme that hydrolyzes galactose from ceramide monohexosides. Deficiency of this enzyme may cause globoid cell leukodystrophy (LEUKODYSTROPHY, GLOBOID CELL). EC 3.2.1.46.Nervous System Physiological Phenomena: Characteristic properties and processes of the NERVOUS SYSTEM as a whole or with reference to the peripheral or the CENTRAL NERVOUS SYSTEM.Chondroitinsulfatases: A group of enzymes that catalyze the hydrolysis of various sulfate bonds of chondroitin sulfate. EC 3.1.6.-.Adenoma, Liver Cell: A benign epithelial tumor of the LIVER.Amylopectin: A highly branched glucan in starch.Sphingolipid Activator Proteins: A family of glycoprotein cofactors that are required for the efficient catabolization of SPHINGOLIPIDS by specific acid hydrolases such as GLUCOSYLCERAMIDASE; GALACTOCEREBROSIDASE; BETA-N-ACETYLHEXOSAMINIDASE; and CEREBROSIDE-SULFATASE.