Linked Life Data

11371512

Source:http://linkedlifedata.com/resource/pubmed/id/11371512

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
2001-5-23
pubmed:abstractText
Sphingolipid activator proteins (saposins A, B, C and D) are small homologous glycoproteins derived from a common precursor protein (prosaposin) encoded by a single gene. They are required for in vivo degradation of sphingolipids with short carbohydrate chains. Six cysteines and one glycosylation site are strictly conserved in all four saposins. Total deficiency of all saposins and specific deficiency of saposin B or C are known among human patients. A mouse model of total saposin deficiency closely mimics the human disease. However, no specific saposin A or D deficiency is known. We introduced an amino acid substitution (C106F) into the saposin A domain by the Cre/loxP system which eliminated one of the three conserved disulfide bonds. Saposin A(-/-) mice developed slowly progressive hind leg paralysis with clinical onset at approximately 2.5 months and survival up to 5 months. Tremors and shaking, prominent in other myelin mutants, were not obvious until the terminal stage. Pathology and analytical biochemistry were qualitatively identical to, but generally much milder than, that seen in the typical infantile globoid cell leukodystrophy (GLD) in man (Krabbe disease) and in several other mammalian species, due to genetic deficiency of lysosomal galactosylceramidase (GALC) (EC 3.2.1.46). Thus, saposin A is indispensable for in vivo degradation of galactosylceramide by GALC. It should now be recognized that, in addition to GALC deficiency, genetic saposin A deficiency could also cause chronic GLD. Genetic saposin A deficiency might be anticipated among human patients with undiagnosed late-onset chronic leukodystrophy without GALC deficiency.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0964-6906
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
10
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1191-9
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:11371512-Amino Acid Substitution, pubmed-meshheading:11371512-Animals, pubmed-meshheading:11371512-Blotting, Southern, pubmed-meshheading:11371512-Body Weight, pubmed-meshheading:11371512-Chronic Disease, pubmed-meshheading:11371512-DNA Primers, pubmed-meshheading:11371512-Galactosylceramidase, pubmed-meshheading:11371512-Gene Targeting, pubmed-meshheading:11371512-Genetic Vectors, pubmed-meshheading:11371512-Genotype, pubmed-meshheading:11371512-Glycoproteins, pubmed-meshheading:11371512-Humans, pubmed-meshheading:11371512-Leukodystrophy, Globoid Cell, pubmed-meshheading:11371512-Lipids, pubmed-meshheading:11371512-Mice, pubmed-meshheading:11371512-Mice, Knockout, pubmed-meshheading:11371512-Mutation, pubmed-meshheading:11371512-Peripheral Nerves, pubmed-meshheading:11371512-Phenotype, pubmed-meshheading:11371512-Polymerase Chain Reaction, pubmed-meshheading:11371512-Psychosine, pubmed-meshheading:11371512-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:11371512-Saposins, pubmed-meshheading:11371512-Sciatic Nerve
pubmed:year
2001
pubmed:articleTitle
A mutation in the saposin A domain of the sphingolipid activator protein (prosaposin) gene results in a late-onset, chronic form of globoid cell leukodystrophy in the mouse.
pubmed:affiliation
Neuroscience Center, Department of Neurology, University of North Carolina, Chapel Hill, NC 27599-7250, USA.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't