Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2006-7-6
pubmed:abstractText
Acquired Fanconi syndrome (FS) is a complication of monoclonal gammopathies featuring a generalized dysfunction of the proximal tubule of the kidney, due to the storage within proximal tubular cells of a monoclonal immunoglobulin light chain. We engineered transgenic mice in which the endogenous mouse Jkappa cluster was replaced by a human VkappaJkappa rearranged gene cloned from a patient with smoldering myeloma-associated FS. The V region belonged to the VkappaI subgroup and was related to the O2-O12 germ-line gene, a V segment previously found associated with FS and light-chain crystallization in several patients with myeloma. Association of the human VkappaI domain with a mouse kappa constant domain in transgenic animals yielded a nephrotoxicity pattern similar to that observed in patients, strongly suggesting that the whole pathogenic effect of FS light chains can be ascribed to a peculiar structure of the V domain. Morphologic alterations of the kidney tubular cells, which contained rhomboid-shape crystals, were observed in mice, together with alterations of the proximal tubule reabsorption function. Moreover, the number of renal crystalline inclusions was dramatically reduced after conditional deletion of the human VkappaI transgene, showing that proximal tubular lesions are reversible upon suppression of the nephrotoxic light chain secretion.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0006-4971
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
108
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
536-43
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
Role of the monoclonal kappa chain V domain and reversibility of renal damage in a transgenic model of acquired Fanconi syndrome.
pubmed:affiliation
Laboratoire d'Immunologie, Centre National de la Recherche Scientifique (CNRS) Unite Mixté de Recherche (UMR) 6101, Equipe labellisée La Ligue, Centre Hospitalier Universitaire (CHU) Dupuytren, Université de Limoges, France.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't