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Query: UNIPROT:P15088 (mast cell)
 14,925 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Many years ago, alert observers noticed among thousands of laboratory mice a few individuals that, unlike their littermates, exhibited areas of white spotting on their fur. No one could have predicted then that an effort to understand the basis for these abnormalities would ultimately contribute to the characterization of a receptor (c-kit) and a corresponding ligand (stem cell factor, SCF) that are critical not only to the migration and development of melanocytes, but also to hematopoiesis, gametogenesis, mast cell development, and, perhaps, development of the central nervous system. Nor could anyone have foretold then that this receptor and ligand would be shown to regulate the development of multiple distinct cellular lineages not only in mice, but also in humans and other primates, or that c-kit and its ligand would be found to influence the secretory function of cells bearing this receptor, as well as their development. 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 c-kit and its ligand. This work shows that SCF critically regulates the migration and survival of mast cell precursors, promotes the proliferation of both immature and mature mast cells, enhances mast cell maturation, directly induces secretion of mast cell mediators, and can regulate the extent of mediator release in mast cells activated by IgE-dependent mechanisms. Indeed, SCF may well prove to be one of the most important of the factors influencing mast cell numbers, phenotype, and function in both health and disease. It now seems virtually certain that further studies of c-kit and SCF will produce important new insights into problems as diverse as the regulation of lineage commitment during normal hematopoiesis or the development and function of the central nervous system. And even though an effect on mast cell development was one of the last phenotypic abnormalities to be recognized in mice with mutations affecting the genes encoding c-kit or SCF, mast cells will continue to represent an important model system for analyzing the biology of c-kit and its ligand.
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PMID:The c-kit receptor, stem cell factor, and mast cells. What each is teaching us about the others. 768 64

Manipulation of the mouse genome has emerged as an important approach for studying gene function and establishing human disease models. In this study, the mouse mutants were generated through N-ethyl-N-nitrosourea (ENU)-induced mutagenesis in C57BL/6J mice. The screening for dominant mutations yielded several mice with fur color abnormalities. One of them causes a phenotype similar to that shown by dominant-white spotting (W) allele mutants. This strain was named Wads because the homozygous mutant mice are white color, anemic, deaf, and sterile. The new mutation was mapped to 42 cM on chromosome five, where proto-oncogene c-kit resides. Sequence analysis of c-kit cDNA from Wads(m/m) revealed a unique T-to-C transition mutation that resulted in Phe-to-Ser substitution at amino acid 856 within a highly conserved tyrosine kinase domain. Compared with other c-kit mutants, Wads may present a novel loss-of-function or hypomorphic mutation. In addition to the examination of adult phenotypes in hearing loss, anemia, and mast cell deficiency, we also detected some early developmental defects during germ cell differentiation in the testis and ovary of neonatal Wads(m/m) mice. Therefore, the Wads mutant may serve as a new disease model of human piebaldism, anemia, deafness, sterility, and mast cell diseases.
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PMID:Identification of a novel point mutation of mouse proto-oncogene c-kit through N-ethyl-N-nitrosourea mutagenesis. 1573 17

Human mast cells have been shown to release histamine in response to the neuropeptide alpha-melanocyte-stimulating hormone (alpha-MSH), but it is unknown whether these cells express proopiomelanocortin (POMC) or POMC-derived peptides. We therefore examined highly purified human skin mast cells and a leukemic mast cell line-1 (HMC-1) for their ability to express POMC and members of the prohormone convertase (PC) family known to process POMC. Furthermore, we investigated whether these cells store and secrete alpha-MSH. Reverse transcriptase-PCR (RT-PCR) analysis revealed that both skin mast cells and HMC-1 cells express POMC mRNA and protein. Expression of the POMC gene at the RNA level in HMC-1 cells could be confirmed by Northern blotting. Transcripts for both PC1 and furin convertase were detectable in skin-derived mast cells and HMC-1 cells, as shown by RT-PCR. In contrast, PC2 transcripts were detected only in skin mast cells, whereas transcripts for paired basic amino acid converting enzyme 4 (PACE4) were present only in HMC-1 cells. Radioimmunoassays performed on cell lysates and cell culture supernatants from human skin-derived mast cells disclosed immunoreactive amounts of alpha-MSH in both fractions. Stimulation with an anti-IgE antibody significantly reduced intracellular alpha-MSH and increased extracellular levels, indicating IgE-mediated secretion of this neuropeptide. Our findings show that human mast cells are active players in the cutaneous POMC system. Mast cell-derived alpha-MSH may contribute to cutaneous hyperpigmentation as seen in patients with urticaria pigmentosa. Moreover, IgE-dependent release of alpha-MSH suggests an immunomodulatory role of this neurohormone during inflammatory and allergic reactions of the skin.
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PMID:Human mast cells in the neurohormonal network: expression of POMC, detection of precursor proteases, and evidence for IgE-dependent secretion of alpha-MSH. 1691 90

High serum IgE levels are characteristic of allergic diseases and immune responses to nematode parasites. A murine allergy model based on infestation with the fur mites Myocoptes musculinus and Myobia musculi was investigated. Analysis of mite infestation in various knockout mice revealed that IgE production in response to these ectoparasites was dependent on T cells, IL-4, and CD40L. Secretion of IL-4 by CD4+ T cells obtained from peripheral LN draining mite-infested skin sites was increased with progressing mite infestation and correlated with the serum IgE induction. A time course analysis of the mRNA expression of switched IgE, activation-induced cytidine deaminase (AID), and epsilon germ-line transcripts (epsilonGLT) suggested that switching to IgE in response to fur mites occurred initially in skin-draining LN. In addition, mite infestation induced mast cell degranulation in the skin as well as mast cell infiltration into skin-draining LN. Analysis of the immune response generated in mite-infested mice is a valuable model for the investigation of allergic disorders and provides information for better understanding of mechanisms involved in IgE induction and regulation in a physiological way of allergen-exposure resembling atopic sensitization in humans.
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PMID:Induction of IgE and allergic-type responses in fur mite-infested mice. 1690 33

The domestic dog is becoming an increasingly valuable model species in medical genetics, showing particular promise to advance our understanding of cancer and orthopaedic disease. Here we undertake the largest canine genome-wide association study to date, with a panel of over 4,200 dogs genotyped at 180,000 markers, to accelerate mapping efforts. For complex diseases, we identify loci significantly associated with hip dysplasia, elbow dysplasia, idiopathic epilepsy, lymphoma, mast cell tumour and granulomatous colitis; for morphological traits, we report three novel quantitative trait loci that influence body size and one that influences fur length and shedding. Using simulation studies, we show that modestly larger sample sizes and denser marker sets will be sufficient to identify most moderate- to large-effect complex disease loci. This proposed design will enable efficient mapping of canine complex diseases, most of which have human homologues, using far fewer samples than required in human studies.
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PMID:Complex disease and phenotype mapping in the domestic dog. 2679 39