Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
1998-5-21
pubmed:abstractText
Junctional epidermolysis bullosa (JEB) is an autosomal recessive skin blistering disease with both lethal and nonlethal forms, with most patients shown to have defects in laminin-5. We analyzed the location of mutations, gene expression levels, and protein chain assembly of the laminin-5 heterotrimer in six JEB patients to determine how the type of genetic lesion influences the pathophysiology of JEB. Mutations within laminin-5 genes were diversely located, with the most severe forms of JEB correlating best with premature termination codons, rather than mapping to any particular protein domain. In all six JEB patients, the laminin-5 assembly intermediates we observed were as predicted by our previous work indicating that the alpha3beta3gamma2 heterotrimer assembles intracellularly via a beta3gamma2 heterodimer intermediate. Since assembly precedes secretion, mutations that disrupt protein-protein interactions needed for assembly are predicted to limit the secretion of laminin-5, and likely to interfere with function. However, our data indicate that typically the most severe mutations diminish mRNA stability, and serve as functional null alleles that block chain assembly by resulting in either a deficiency (in the nonlethal mitis variety) or a complete absence (in lethal Herlitz-JEB) of one of the chains needed for laminin-5 heterotrimer assembly.
pubmed:grant
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/9547338-1375393, http://linkedlifedata.com/resource/pubmed/commentcorrection/9547338-1376637, http://linkedlifedata.com/resource/pubmed/commentcorrection/9547338-1383240, http://linkedlifedata.com/resource/pubmed/commentcorrection/9547338-1401088, http://linkedlifedata.com/resource/pubmed/commentcorrection/9547338-1420180, http://linkedlifedata.com/resource/pubmed/commentcorrection/9547338-1485969, http://linkedlifedata.com/resource/pubmed/commentcorrection/9547338-1517226, http://linkedlifedata.com/resource/pubmed/commentcorrection/9547338-1556112, http://linkedlifedata.com/resource/pubmed/commentcorrection/9547338-1680286, http://linkedlifedata.com/resource/pubmed/commentcorrection/9547338-1847260, http://linkedlifedata.com/resource/pubmed/commentcorrection/9547338-1860885, http://linkedlifedata.com/resource/pubmed/commentcorrection/9547338-1999509, http://linkedlifedata.com/resource/pubmed/commentcorrection/9547338-2273105, http://linkedlifedata.com/resource/pubmed/commentcorrection/9547338-2398889, http://linkedlifedata.com/resource/pubmed/commentcorrection/9547338-2431136, http://linkedlifedata.com/resource/pubmed/commentcorrection/9547338-2436931, http://linkedlifedata.com/resource/pubmed/commentcorrection/9547338-2454667, http://linkedlifedata.com/resource/pubmed/commentcorrection/9547338-2556677, http://linkedlifedata.com/resource/pubmed/commentcorrection/9547338-2779551, http://linkedlifedata.com/resource/pubmed/commentcorrection/9547338-3771648, http://linkedlifedata.com/resource/pubmed/commentcorrection/9547338-3840485, http://linkedlifedata.com/resource/pubmed/commentcorrection/9547338-7504435, http://linkedlifedata.com/resource/pubmed/commentcorrection/9547338-7512558, http://linkedlifedata.com/resource/pubmed/commentcorrection/9547338-7550237, http://linkedlifedata.com/resource/pubmed/commentcorrection/9547338-7559513, http://linkedlifedata.com/resource/pubmed/commentcorrection/9547338-7594636, http://linkedlifedata.com/resource/pubmed/commentcorrection/9547338-7633458, http://linkedlifedata.com/resource/pubmed/commentcorrection/9547338-7698759, http://linkedlifedata.com/resource/pubmed/commentcorrection/9547338-7706759, http://linkedlifedata.com/resource/pubmed/commentcorrection/9547338-7706760, http://linkedlifedata.com/resource/pubmed/commentcorrection/9547338-7849725, http://linkedlifedata.com/resource/pubmed/commentcorrection/9547338-7861013, http://linkedlifedata.com/resource/pubmed/commentcorrection/9547338-7921537, http://linkedlifedata.com/resource/pubmed/commentcorrection/9547338-8012393, http://linkedlifedata.com/resource/pubmed/commentcorrection/9547338-8012394, http://linkedlifedata.com/resource/pubmed/commentcorrection/9547338-8077230, http://linkedlifedata.com/resource/pubmed/commentcorrection/9547338-8113417, http://linkedlifedata.com/resource/pubmed/commentcorrection/9547338-8306988, http://linkedlifedata.com/resource/pubmed/commentcorrection/9547338-8358428, http://linkedlifedata.com/resource/pubmed/commentcorrection/9547338-8586427, http://linkedlifedata.com/resource/pubmed/commentcorrection/9547338-8612705, http://linkedlifedata.com/resource/pubmed/commentcorrection/9547338-8618058, http://linkedlifedata.com/resource/pubmed/commentcorrection/9547338-8824879, http://linkedlifedata.com/resource/pubmed/commentcorrection/9547338-9217810
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0022-1007
pubmed:author
pubmed:issnType
Print
pubmed:day
20
pubmed:volume
187
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1273-83
pubmed:dateRevised
2009-11-18
pubmed:meshHeading
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