Linked Life Data

10408385

Source:http://linkedlifedata.com/resource/pubmed/id/10408385

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1-3
pubmed:dateCreated
1999-9-15
pubmed:abstractText
Crry is a potent complement regulator that inhibits classical and alternative pathway C3 convertases in rodents. We have produced transgenic animals expressing Crry as a recombinant soluble protein driven by the broadly active metallothionein-I promoter. These animals have high serum and urinary levels of rsCrry leading to inhibition of complement activity. In nephrotoxic serum nephritis (NSN), injected antibodies bind to glomeruli, leading to complement activation and subsequent glomerular injury and albuminuria. We have shown that rsCrry can block such injury and reduce albuminuria by as much as 75%. Corresponding to the reduction in albuminuria was the complete absence of C3 staining in glomeruli by immunofluorescence microscopy in 17/20 transgene positive animals. Support for a local source of protective rsCrry in this model is provided by the demonstration of Crry transgene mRNA in the glomerulus and a very high fractional excretion of rsCrry in the urine. Therefore, rsCrry expression markedly ameliorates an antibody-induced disease model in vivo. In addition, local synthesis of Crry in other organs that are targets of immune injury has been found. For example, Crry transgene mRNA is present throughout the central nervous system and in pancreatic islets. Thus, continuous complement inhibition at the C3 convertase step appears to be feasible and is effective in complement-mediated injury states. A number of disease models affecting these target organs can be tested using these mice.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0162-3109
pubmed:author
pubmed:issnType
Print
pubmed:volume
42
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
245-54
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1999
pubmed:articleTitle
Renal, central nervous system and pancreatic overexpression of recombinant soluble Crry in transgenic mice. A novel means of protection from complement-mediated injury.
pubmed:affiliation
Department of Medicine, The University of Chicago, IL 60637, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't