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Mast cell hyperplasia, B-cell malignancy, and intestinal inflammation in mice with conditional expression of a constitutively active kit

Gerbaulet, Alexander, Wickenhauser, Claudia, Scholten, Julia, Peschke, Katrin, Drube, Sebastian, Horny, Hans-Peter, Kamradt, Thomas, Naumann, Ronald, Müller, Werner, Krieg, Thomas, Waskow, Claudia, Hartmann, Karin, Roers, Axel·2011·Blood
DOI 10.1182/blood-2008-11-189605
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Abstract

Signaling through the receptor tyrosine kinase kit controls proliferation and differentiation of hematopoietic precursor cells and mast cells. Somatic point mutations of the receptor that constitutively activate kit signaling are associated with mastocytosis and various hematopoietic malignancies. We generated a Cre/loxP-based bacterial artificial chromosome transgenic mouse model that allows conditional expression of a kit gene carrying the kitD814V mutation (the murine homolog of the most common mutation in human mastocytosis, kitD816V) driven by the kit promoter. Expression of the mutant kit in cells of adult mice, including hematopoietic precursors, caused severe mastocytosis with 100% penetrance at young age frequently associated with additional hematopoietic (mostly B lineage–derived) neoplasms and focal colitis. Restriction of transgene expression to mature mast cells resulted in a similar mast cell disease developing with slower kinetics. Embryonic expression led to a hyperproliferative dysregulation of the erythroid lineage with a high rate of perinatal lethality. In addition, most adult animals developed colitis associated with mucosal mast cell accumulation. Our findings demonstrate that the effects of constitutive kit signaling critically depend on the developmental stage and the state of differentiation of the cell hit by the gain-of-function mutation.

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Metadata

Authors
Gerbaulet, A., Wickenhauser, C., Scholten, J., Peschke, K., Drube, S., Horny, H.-P., Kamradt, T., Naumann, R., Müller, W., Krieg, T., Waskow, C., Hartmann, K., & Roers, A.
Venue
Blood
Publisher
American Society of Hematology
Published
2011-02-10
Volume
117
Issue
6
Pages
2012-2021
ISSN
  • 0006-4971
  • 1528-0020
DOI
10.1182/blood-2008-11-189605
Cited by
64
References
1
Language
en

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CoChat. (2026). Citation check: Mast cell hyperplasia, B-cell malignancy, and intestinal inflammation in mice with conditional expression of a constitutively active kit. https://app.cochat.ai/papers/10.1182/blood-2008-11-189605
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Gerbaulet, A., Wickenhauser, C., Scholten, J., Peschke, K., Drube, S., Horny, H.-P., Kamradt, T., Naumann, R., Müller, W., Krieg, T., Waskow, C., Hartmann, K., & Roers, A. (2011). Mast cell hyperplasia, B-cell malignancy, and intestinal inflammation in mice with conditional expression of a constitutively active kit. Blood. https://doi.org/10.1182/blood-2008-11-189605