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Tissue‐selective mast cell reconstitution and differential lung gene expression in mast cell‐deficient Kit W‐sh / Kit W‐sh sash mice
Abstract
Summary: Background Mast cell‐deficient Kit W / Kit W‐v mice are an important resource for studying mast cell functions in vivo . However, because they are compound heterozygotes in a mixed genetic background and are infertile, they cannot be crossed easily with other mice. Objective To overcome this limitation, we explored the use of Kit W‐sh / Kit W‐sh mice for studying mast cell biology in vivo . Results These mice are in a C57BL/6 background, are fertile and can be bred directly with other genetically modified mice. Ten‐week‐old Kit W‐sh / Kit W‐sh are profoundly mast cell‐deficient. No mast cells are detected in any major organ, including the lung. Gene microarrays detect differential expression of just seven of 16 463 genes in lungs of Kit W‐sh / Kit W‐sh mice compared with wild‐type mice, indicating that resting mast cells regulate expression of a small set of genes in the normal lung. Injecting 10 7 bone marrow‐derived mast cells (BMMC) into tail veins of Kit W‐sh / Kit W‐sh mice reconstitutes mast cell populations in lung, stomach, liver, inguinal lymph nodes, and spleen, but not in the tongue, trachea or skin. Injection of BMMC into ear dermis or peritoneum reconstitutes mast cells locally in these tissues. When splenectomized Kit W‐sh / Kit W‐sh mice are intravenously injected with BMMC, mast cells circulate longer and are found more often in the liver and inguinal lymph nodes, indicating that the spleen acts as a reservoir for mast cells following injection and limits migration to some tissues. Conclusion In summary, these findings show that mast cell‐deficient Kit W‐sh / Kit W‐sh mice possess unique attributes that favour their use for studying mast cell functions in vivo .
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“In addition to using the original mast cell-deficient WBB6F1-KitW/KitW-v mice to prepare “mast cell knock-in mice”, this approach also can be employed using C57BL/6-KitW-sh/KitW-sh mice, which have the advantage of being inbred, fertile and not anemic [68, 69, 73].”
From Mast cells and IgE in defense against lethality of venoms: Possible “benefit” of allergy (2020) · cites this paper as [69]
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Inflammatory mast cells up-regulate angiogenesis during squamous epithelial carcinogenesis
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“mast cells have been implicated in the pathogenesis of asthma [9], arthritis [10], experimental allergic encephalitis [11], experimental bullous pemphigoid [12], cancer progression [ 13 ], and defence against bacterial infections [14, 15].”
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Liu, J., Divoux, A., Sun, J., Zhang, J., Clément, K., Glickman, J. N., Sukhova, G. K., Wolters, P. J., Du, J., Gorgun, C. Z., et al. (2009) · Nature Medicine · doi:10.1038/nm.1994 · Cited by 796
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Self-citationMast cells and IgE in defense against venoms: Possible “good side” of allergy?
Galli, S. J., Starkl, P., Marichal, T., & Tsai, M. (2016) · Allergology International · doi:10.1016/j.alit.2015.09.002 · Cited by 73
Anaphylaxis: Mechanisms of Mast Cell Activation
Kalesnikoff, J., & Galli, S. J. (2010) · Chemical Immunology and Allergy · doi:10.1159/000315937 · Cited by 67
Mast cells and IgE in defense against lethality of venoms: Possible “benefit” of allergy
Galli, S. J., Metz, M., Starkl, P., Marichal, T., & Tsai, M. (2020) · Allergo Journal International · doi:10.1007/s40629-020-00118-6 · Cited by 57
Metadata
- Authors
- Wolters, P. J., Clair, J. M., Lewis, C. C., Villalta, S. A., Baluk, P., Erle, D. J., & Caughey, G. H.
- Venue
- Clinical & Experimental Allergy
- Publisher
- Wiley
- Published
- 2005-01
- Volume
- 35
- Issue
- 1
- Pages
- 82-88
- ISSN
- 0954-7894
- 1365-2222
- Cited by
- 131
- References
- 1
- Language
- en
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- Wolters, P. J., Clair, J. M., Lewis, C. C., Villalta, S. A., Baluk, P., Erle, D. J., & Caughey, G. H. (2005). Tissue‐selective mast cell reconstitution and differential lung gene expression in mast cell‐deficient Kit W‐sh / Kit W‐sh sash mice. Clinical & Experimental Allergy. https://doi.org/10.1111/j.1365-2222.2005.02136.x
