Mast cell-deficient W-sash c-kit mutant Kit W-sh/W-sh mice as a model for investigating mast cell biology in vivo.
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.
Grimbaldeston
Michele A
MA
Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305-5324, USA.
Chen
Ching-Cheng
CC
Piliponsky
Adrian M
AM
Tsai
Mindy
M
Tam
See-Ying
SY
Galli
Stephen J
SJ
D000818:Animals; D001655:Bile Reflux / Q000235:genetics; D001854:Bone Marrow Cells / Q000166:cytology / Q000473:pathology; D002454:Cell Differentiation; D008214:Lymphocytes / Q000473:pathology; D008407:Mast Cells / Q000166:cytology / Q000473:pathology* / Q000502:physiology* / Q000637:transplantation; D051379:Mice; D020297:Mice, Congenic; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D023421:Models, Animal; D009154:Mutation; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics* / Q000378:metabolism
D019009:Proto-Oncogene Proteins c-kit