{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T19:27:12Z","timestamp":1791487632298,"version":"4.3.4"},"reference-count":30,"publisher":"Rockefeller University Press","issue":"12","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2005,12,19]]},"abstract":"<jats:p>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\u2013derived MCs from transgenic animals can be maintained in culture for &amp;gt;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.<\/jats:p>","DOI":"10.1084\/jem.20050807","type":"journal-article","created":{"date-parts":[[2005,12,13]],"date-time":"2005-12-13T21:38:42Z","timestamp":1134509922000},"page":"1635-1641","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":83,"title":["Mastocytosis in mice expressing human Kit receptor with the activating Asp816Val mutation"],"prefix":"10.1084","volume":"202","author":[{"given":"Jacques P.","family":"Zappulla","sequence":"first","affiliation":[{"name":"1Institut National de la Sante\u0301 et de la Recherche Me\u0301dicale (INSERM) U563, Centre de Physiopathologie de Toulouse Purpan, Purpan Hospital, 31000 Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrice","family":"Dubreuil","sequence":"additional","affiliation":[{"name":"2INSERM U599, Marseille Institute for Cancer, 13009 Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabine","family":"Desbois","sequence":"additional","affiliation":[{"name":"1Institut National de la Sante\u0301 et de la Recherche Me\u0301dicale (INSERM) U563, Centre de Physiopathologie de Toulouse Purpan, Purpan Hospital, 31000 Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Se\u0301bastien","family":"Le\u0301tard","sequence":"additional","affiliation":[{"name":"2INSERM U599, Marseille Institute for Cancer, 13009 Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadine Ben","family":"Hamouda","sequence":"additional","affiliation":[{"name":"3Centre National de la Recherche Scientifique UMR 8147, Cellular and Molecular Hematology Laboratory, Pharmacy University, 75006 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Dae\u0308ron","sequence":"additional","affiliation":[{"name":"4Cellular and Molecular Allergology Laboratory, Pasteur Institute, 75015 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georges","family":"Delsol","sequence":"additional","affiliation":[{"name":"1Institut National de la Sante\u0301 et de la Recherche Me\u0301dicale (INSERM) U563, Centre de Physiopathologie de Toulouse Purpan, Purpan Hospital, 31000 Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michel","family":"Arock","sequence":"additional","affiliation":[{"name":"3Centre National de la Recherche Scientifique UMR 8147, Cellular and Molecular Hematology Laboratory, Pharmacy University, 75006 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roland S.","family":"Liblau","sequence":"additional","affiliation":[{"name":"1Institut National de la Sante\u0301 et de la Recherche Me\u0301dicale (INSERM) U563, Centre de Physiopathologie de Toulouse Purpan, Purpan Hospital, 31000 Toulouse, France"},{"name":"5Immunology Laboratory, Rangueil University Hospital, 31000 Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2005,12,13]]},"reference":[{"key":"2023072513065722800_BIB1","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1038\/320415a0","volume":"320","year":"1986","journal-title":"Nature."},{"key":"2023072513065722800_BIB2","doi-asserted-by":"crossref","first-page":"744","DOI":"10.1046\/j.0007-1048.2001.03294.x","volume":"116","year":"2002","journal-title":"Br. 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