title: Mastocytosis in mice expressing human Kit receptor with the activating Asp816Val mutation.
abstract: Mastocytosis is a rare neoplastic disease characterized by a pathologic accumulation of tissue mast cells (MCs). Mastocytosis is often associated with a somatic point mutation in the Kit protooncogene leading to an Asp/Val substitution at position 816 in the kinase domain of this receptor. The contribution of this mutation to mastocytosis development remains unclear. In addition, the clinical heterogeneity presented by mastocytosis patients carrying the same mutation is unexplained. We report that a disease with striking similarities to human mastocytosis develops spontaneously in transgenic mice expressing the human Asp816Val mutant Kit protooncogene specifically in MCs. This disease is characterized by clinical signs ranging from a localized and indolent MC hyperplasia to an invasive MC tumor. In addition, bone marrow-derived MCs from transgenic animals can be maintained in culture for >24 mo and acquire growth factor independency for proliferation. These results demonstrate a causal link in vivo between the Asp816Val Kit mutation and MC neoplasia and suggest a basis for the clinical heterogeneity of human mastocytosis.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale U563, Centre de Physiopathologie de Toulouse Purpan, Purpan Hospital, 31000 Toulouse, France.
authors.forename: Jacques P
authors.initials: JP
authors.lastname: Zappulla
authors.forename: Patrice
authors.initials: P
authors.lastname: Dubreuil
authors.forename: Sabine
authors.initials: S
authors.lastname: Desbois
authors.forename: Sébastien
authors.initials: S
authors.lastname: Létard
authors.forename: Nadine Ben
authors.initials: NB
authors.lastname: Hamouda
authors.forename: Marc
authors.initials: M
authors.lastname: Daëron
authors.forename: Georges
authors.initials: G
authors.lastname: Delsol
authors.forename: Michel
authors.initials: M
authors.lastname: Arock
authors.forename: Roland S
authors.initials: RS
authors.lastname: Liblau
mesh_terms: D000818:Animals; D015153:Blotting, Western; D018929:Cell Culture Techniques; D017931:DNA Primers; D006801:Humans; D008407:Mast Cells / Q000378:metabolism*; D008415:Mastocytosis / Q000235:genetics* / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D020125:Mutation, Missense / Q000235:genetics*; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D017931:DNA Primers; D019009:Proto-Oncogene Proteins c-kit