Publisher Summary This chapter focuses on the importance of stem cell factor (SCF) and the stem cell factor receptor (SCFR) in hematopoiesis and other complex developmental programs affecting melanocytes, germ cells, and mast cells that are predicted based on an analysis of the phenotype of mice with mutations affecting SCF or its receptor. Investigation of the effects of SCF on a single cell type, the mast cell, has produced the most complete picture of the spectrum of biological processes that can be regulated by interactions between the SCFR and SCF. This work shows that SCF critically regulates the migration and survival of mast cell precursors and mast cell adherence, promotes the proliferation of both immature and mature mast cells, enhances mast cell maturation, directly induces secretion of mast cell mediators, and regulates the extent of mediator release in mast cells activated by immunoglobulin (IgE)-dependent mechanisms. SCF also has a major role in lymphohematopoiesis. Notably, many of the actions of SCF in hematopoiesis and in lymphocyte development, including effects on the survival and proliferation of early hematopoietic cells, as well as actions that augment the maturation/differentiation of diverse lineages of hematopoietic or lymphoid cells, are expressed in large part through synergistic interactions with other growth factors.

The kit ligand, stem cell factor

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 KitW/W-v mice impair melanogenesis and result in anemia, sterility, and markedly reduced levels of tissue mast cells. In contrast, KitW-sh/W-sh mice, bearing the W-sash (Wsh) inversion mutation, have mast cell deficiency but lack anemia and sterility. We report that adult KitW-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 KitW/W-v mice, KitW-sh/W-sh mice had normal numbers of TCRγδ intraepithelial lymphocytes in the intestines and did not exhibit a high incidence of idiopathic dermatitis, ulcers, or squamous papillomas of the stomach, but like KitW/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 KitW-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, KitW-sh/W-sh mice represent a useful model for mast cell research, especially for analyzing mast cell function in vivo.

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

:CD117 (KIT) is a type III receptor tyrosine kinase operating in cell signal transduction in several cell types. Normally KIT is activated (phosphorylated) by binding of its ligand, the stem cell factor. This leads to a phosphorylation cascade ultimately activating various transcription fact

KIT (CD117): a review on expression in normal and neoplastic tissues, and mutations and their clinicopathologic correlation.

https://www.gastrojournal.org/article/S0016-5085(02)00215-9/pdf

Kyoji Kondo

Papers

Anemia and mast cell depletion in mutant rats that are homozygous at "white spotting (Ws)" locus.