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| HAL: hal-00016364, version 1 |
| PubMed: 16352739 |
| PubMed Central: 2212965 |
| DOI: 10.1084/jem.20050807 |
| Detailed view |  Export this paper |
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| Journal of Experimental Medicine / The Journal of Experimental Medicine 202, 12 (2005) 1635-41 |
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| Mastocytosis in mice expressing human Kit receptor with the activating Asp816Val mutation. |
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| Jacques P. Zappulla 1Patrice Dubreuil 2 |
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| (2005-12-19) |
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| 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. |
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| 1: | Centre de Physiopathologie Toulouse Purpan |
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INSERM : U563 – IFR30 – Université Paul Sabatier - Toulouse III – IFR150 |
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| 2: | Cancérologie |
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INSERM : U599 – Institut Paoli-Calmettes – Université de la Méditerranée - Aix-Marseille II |
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| 3: | Cytokines, hématopoïèse et réponse immune (CHRI) |
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CNRS : UMR8147 – Université Paris V - Paris Descartes |
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| 4: | Allergologie Moléculaire et Cellulaire |
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INSERM : U760 – Institut Pasteur de Paris |
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| 5: | Laboratoire d'immunologie |
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Hôpital de Rangueil |
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| Subject | : | Life Sciences/Immunology |
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| hal-00016364, version 1 | |
| http://hal.archives-ouvertes.fr/hal-00016364 | |
| oai:hal.archives-ouvertes.fr:hal-00016364 | |
| From: Catherine Slama | |
| Submitted on: Saturday, 27 February 2010 16:25:42 | |
| Updated on: Sunday, 28 February 2010 07:24:36 | |
