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(American Journal of Pathology. 2005;167:835-848.)
© 2005 American Society for Investigative Pathology

Mast Cell-Deficient W-sash c-kit Mutant Kit^W-sh/W-sh Mice as a Model for Investigating Mast Cell Biology in Vivo

Michele A. Grimbaldeston^*, Ching-Cheng Chen^*, Adrian M. Piliponsky^*, Mindy Tsai^*, See-Ying Tam^* and Stephen J. Galli^*

From the Departments of Pathology^* and Microbiology and Immunology, Stanford University School of Medicine, Stanford, California

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 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.

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