51. Mast cell-deficient W-sash c-kit mutant Kit W-sh/W-sh mice as a model for investigating mast cell biology in vivo
- Author
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See Ying Tam, Stephen J. Galli, Mindy Tsai, Michele A. Grimbaldeston, Ching-Cheng Chen, and Adrian M. Piliponsky
- Subjects
Pathology ,medicine.medical_specialty ,Transgene ,Cellular differentiation ,Bone Marrow Cells ,Mice, Transgenic ,Biology ,Pathology and Forensic Medicine ,symbols.namesake ,Mice ,Mice, Congenic ,medicine ,Animals ,Lymphocytes ,Mast Cells ,Bile Reflux ,Cell Differentiation ,Mast cell ,Molecular biology ,Mice, Mutant Strains ,Interstitial cell of Cajal ,Transplantation ,Original Research Paper ,Haematopoiesis ,Proto-Oncogene Proteins c-kit ,medicine.anatomical_structure ,Models, Animal ,Mutation ,symbols ,Intraepithelial lymphocyte ,Bone marrow - Abstract
Mice carrying certain mutations in the white spotting (W) locus (ie, c-kit) exhibit reduced c-kit tyrosine kinase-dependent signaling that results in mast cell deficiency and other phenotypic abnormalities. The c-kit mutations in Kit(W/W-v) mice impair melanogenesis and result in anemia, sterility, and markedly reduced levels of tissue mast cells. In contrast, Kit(W-sh/W-sh) mice, bearing the W-sash (W(sh)) inversion mutation, have mast cell deficiency but lack anemia and sterility. We report that adult Kit(W-sh/W-sh) mice had a profound deficiency in mast cells in all tissues examined but normal levels of major classes of other differentiated hematopoietic and lymphoid cells. Unlike Kit(W/W-v) mice, Kit(W-sh/W-sh) mice had normal numbers of TCR gammadelta intraepithelial lymphocytes in the intestines and did not exhibit a high incidence of idiopathic dermatitis, ulcers, or squamous papillomas of the stomach, but like Kit(W/W-v) mice, they lacked interstitial cells of Cajal in the gut and exhibited bile reflux into the stomach. Systemic or local reconstitution of mast cell populations was achieved in nonirradiated adult Kit(W-sh/W-sh) mice by intravenous, intraperitoneal, or intradermal injection of wild-type bone marrow-derived cultured mast cells but not by transplantation of wild-type bone marrow cells. Thus, Kit(W-sh/W-sh) mice represent a useful model for mast cell research, especially for analyzing mast cell function in vivo.
- Published
- 2005