title: Mutational analysis in murine models for myeloma-associated Fanconi's syndrome or cast myeloma nephropathy.
abstract: We have designed an in vivo model in which murine hybridoma cell clones producing human Ig light chains (LC) are administered to mice. Depending on which monoclonal LC is expressed, this model mimics either cast myeloma nephropathy or the pathological condition defined as myeloma-associated Fanconi's syndrome (FS) with LC crystallization. Morphological alterations of the kidney cells are thus obtained in mice. All studied LC are closely related human monoclonal VkappaI proteins, which differ by a limited number of substitutions within the variable region. In the case of an FS monoclonal LC, we show that limited changes introduced through site-directed mutagenesis in the variable domain may suppress formation of intracellular crystals within tubular cells. We also show that multiple peculiarities of the variable region are simultaneously needed to allow LC crystallization; this property thus likely results from a unique LC tridimensional conformation imposed by concomitant somatic mutations of a specific germinally encoded framework.
authors.affiliation: Laboratoire d'Immunologie, CNRS EP118, Centre Hospitalier Universitaire de Limoges, Limoges, France.
authors.forename: C
authors.initials: C
authors.lastname: Decourt
authors.forename: A
authors.initials: A
authors.lastname: Rocca
authors.forename: F
authors.initials: F
authors.lastname: Bridoux
authors.forename: F
authors.initials: F
authors.lastname: Vrtovsnik
authors.forename: J L
authors.initials: JL
authors.lastname: Preud'homme
authors.forename: M
authors.initials: M
authors.lastname: Cogné
authors.forename: G
authors.initials: G
authors.lastname: Touchard
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D003460:Crystallization; D004252:DNA Mutational Analysis; D005198:Fanconi Syndrome / Q000235:genetics*; D006801:Humans; D007147:Immunoglobulin Light Chains / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D017386:Sequence Homology, Amino Acid
chemical_list: D007147:Immunoglobulin Light Chains