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Blood, 15 July 2006, Vol. 108, No. 2, pp. 536-543. Prepublished online as a Blood First Edition Paper on March 16, 2006; DOI 10.1182/blood-2005-11-4419. This Article Full Text (PDF) All Versions of this Article: 2005-11-4419v1 108/2/536    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Sirac, C. Articles by Cogne, M. Search for Related Content PubMed PubMed Citation Articles by Sirac, C. Articles by Cogne, M. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted November 9, 2005 Accepted February 28, 2006 Role of the monoclonal chain V domain and reversibility of renal damage in a transgenic model of acquired Fanconi's syndrome Christophe Sirac, Frank Bridoux, Claire Carrion, Olivier Devuyst, Beatrice Fernandez, Jean-Michel Goujon, Chahrazed El Hamel, Jean-Claude Aldigier, Guy Touchard, and Michel Cogne* Laboratoire d'Immunologie, CNRS UMR 6101, Universite de Limoges, Limoges, France Laboratoire d'Immunologie, CNRS UMR 6101, Universite de Limoges, Limoges, France; Service de Nephrologie, CHU Jean Bernard, Poitiers, France Division of Nephrology, NEFR Unit, Universite Catholique de Louvain Medical School, Brussels, Belgium Unite de Pathologie Ultrastructurale et Experimentale, Service d'Anatomie Pathologique, CHU Jean Bernard, Poitiers, France Service de Nephrologie, CHU Jean Bernard, Poitiers, France * Corresponding author; email: cogne{at}unilim.fr. Acquired Fanconi s 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 J cluster was replaced by a human VJ rearranged gene cloned from a patient with smoldering myeloma-associated FS. The V region belonged to the VI subgroup and was related to the O2-O12 germline gene, a V segment previously found associated with FS and light chain crystallization in several myeloma patients. Association of the human VI domain with a mouse 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. Morphological 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 VI transgene, showing that proximal tubular lesions are reversible upon suppression of the nephrotoxic light chain secretion. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Animal models: a pot of gold Guillermo A. Herrera Blood 2006 108: 414. [Full Text] [PDF] This article has been cited by other articles: G. Merlini and M. J. Stone Dangerous small B-cell clones Blood, October 15, 2006; 108(8): 2520 - 2530. [Abstract] [Full Text] [PDF]

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